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Yang Y, Xin M, Huang L, Hao Y, Xu M. A novel coumarin-incorporated lanthanide coordination nanoprobe for ratiometric sensing of tetracycline. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 337:126108. [PMID: 40147397 DOI: 10.1016/j.saa.2025.126108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/13/2025] [Accepted: 03/22/2025] [Indexed: 03/29/2025]
Abstract
Tetracycline (Tc), a broad-spectrum antibiotic for treating bacterial infections, poses significant risks to human health and the environment. This study presents a novel lanthanide coordination probe, AMP/Eu/CMP, for the ratiometric detection of Tc. The pyridine-appended coumarin derivative, CMP, acting as a stable internal reference, combines with AMP and Eu3+ to form the robust ratiometric probe AMP/Eu/CMP. Upon binding to Tc, Eu3+ fluorescence (emission at 616 nm) is sensitized while CMP fluorescence (emission at 505 nm) remains unchanged, resulting in a clear fluorescence shift from blue-green to red, enabling effective ratiometric detection of Tc. By integrating a smartphone color recognition app, rapid and visual detection of tetracycline concentrations is achieved. Additionally, paper-based test strips were developed for on-site Tc detection, exhibiting a linear response across a wide concentration range, making this method suitable for applications in food safety, pharmaceutical analysis, and environmental monitoring. The use of a fluorescent molecule with unique photophysical properties as an internal reference enables the construction of a high-performance, ratiometric lanthanide coordination polymer probe that is rapid, simple, and cost-effective, providing valuable insights for the development of future fluorescence sensors.
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Affiliation(s)
- Yufei Yang
- College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China
| | - Menglin Xin
- School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China
| | - Lijie Huang
- College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China
| | - Yuanqiang Hao
- College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China; School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.
| | - Maotian Xu
- College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China.
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2
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Qin Z, Peng T, Qin X, Liu G, Zhang H. Colorimetric/fluorescent dual-mode biosensor based on metalloporphyrin covalently modified NH 2-MIL-101(Fe) with highly efficient peroxidase-like activity for the detection of tetracycline in honey samples. Food Chem 2025; 484:144387. [PMID: 40273871 DOI: 10.1016/j.foodchem.2025.144387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 03/21/2025] [Accepted: 04/16/2025] [Indexed: 04/26/2025]
Abstract
Accurate detection of tetracycline residue is of great significance for ensuring product quality and protecting human health. Here, a colorimetric/fluorescent dual-mode biosensor was developed for the detection of tetracycline in honey by using metalloporphyrin [TCPP(Fe)] covalently modified NH2-MIL-101(Fe) [named NH2-MIL-101(Fe)@TCPP(Fe)]. The morphology, chemical structure and peroxidas-like activity of this hybrid nanozyme were comprehensively studied. Based on excellent catalytic activity and intrinsic fluorescence of NH2-MIL-101(Fe)@TCPP(Fe), a colorimetric/fluorescent dual-mode biosensor was developed for the detection of tetracycline. The primary mechanism for this dual mode biosensor was the inhibitory effect of tetracycline on on NH2-MIL-101(Fe)@TCPP(Fe) catalyzed chromatic reaction between H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB)/o-phenylenediamine (OPD), which was ascribed to the consumption of ·OH by tetracycline and the adsorption of tetracycline on the surface of NH2-MIL-101(Fe)@TCPP(Fe). After effective validation, this colorimetric/fluorescent dual mode method was applied to detect tetracycline residues in three actual honey samples.
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Affiliation(s)
- Zhiyang Qin
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Tianyue Peng
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Xinguang Qin
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Gang Liu
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Haizhi Zhang
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
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3
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Frankowski R, Płatkiewicz J, Kowalska M, Grześkowiak T, Pruss A, Zgoła-Grześkowiak A. The efficiency of biodegradation processes for removal of tetracycline antibacterial drugs using activated sludge and river water inocula. JOURNAL OF ENVIRONMENTAL HEALTH SCIENCE & ENGINEERING 2025; 23:13. [PMID: 40226514 PMCID: PMC11992300 DOI: 10.1007/s40201-025-00940-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 03/26/2025] [Indexed: 04/15/2025]
Abstract
Purpose Tetracycline, chlortetracycline, and oxytetracycline are commonly prescribed antibiotics. Their extensive use results in a large stream of tetracyclines entering wastewater treatment plants (WWTPs). However, they can still be found in surface waters, which may suggest their incomplete removal in the WWTPs. The study was designed to show (i) how much of tetracyclines may be removed before they enter the environment, (ii) how tetracyclines may be removed after they enter surface water, (iii) how the presence of tetracyclines influence the metabolic activity of bacteria. Method Degradation of tetracyclines was studied using two types of inoculum, simulating degradation in WWTPs and rivers. Cell metabolic activity was assessed to show potential risks arising from their appearance in water. Results Complete primary degradation in the test with wastewater sludge inoculum was achieved within not more than 14 days. In the test with river water inoculum removal of both tetracycline and oxytetracycline did not exceed 20% in 28 days. Chlortetracycline was transformed rapidly but without considerable structural change. Although no considerable removal was achieved, bacterial activity in the river water test after 28 days was 10 times greater than while starting the test. Conclusions The study shows that appropriate retention of sewage in WWTPs must be provided. Otherwise, tetracyclines will accumulate in the environment, where their removal is limited, even though bacterial activity is still relatively high.
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Affiliation(s)
- Robert Frankowski
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
| | - Julia Płatkiewicz
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
| | - Marta Kowalska
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
| | - Tomasz Grześkowiak
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
| | - Alina Pruss
- Institute of Environmental Engineering and Building Installations, Faculty of Environmental and Power Engineering, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
| | - Agnieszka Zgoła-Grześkowiak
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, Poznań, 60-965 Poland
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4
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Haeili M, Aghajanzadeh M, Moghaddasi K, Omrani M, Ghodousi A, Cirillo DM. Emergence of transferable tigecycline and eravacycline resistance gene tet(X4) in Escherichia coli isolates from Iran. Sci Rep 2025; 15:16581. [PMID: 40360684 PMCID: PMC12075785 DOI: 10.1038/s41598-025-98206-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 04/10/2025] [Indexed: 05/15/2025] Open
Abstract
Tigecycline (TGC) and eravacycline (ERV) are critical last-resort antibiotics used to treat complicated infections caused by extensively drug-resistant Gram-negative bacteria particularly carbapenem- and colistin-resistant Enterobacterales. The recent emergence of plasmid-mediated TGC resistance gene tet(X) in Enterobacterales of both animal and human origins represents a significant public health threat. In this study, we characterized tet(X4)-bearing Escherichia coli isolates recovered from cattle fecal samples in Iran. A total of 395 fecal samples obtained from calves were screened for tigecycline-resistant (TGC-R) E. coli by inoculating in to selective culture media containing tigecycline. The presence of tet(X) gene among the recovered TGC-R enteric bacteria was assessed using PCR. Genetic relatedness of the tet(X)-bearing strains was analyzed via ERIC-PCR. Three tet(X)-bearing strains were further characterized by whole genome sequencing (WGS) using Illumina platform. The transferability and stability of tet(X)-bearing elements were evaluated by conjugation assay and successive subculturing on antibiotic-free culture media respectively. A total of five tet(X)-positive E. coli isolates exhibiting high-level resistance to tigecycline (MIC = 64 mg/L) and eravacycline (MIC > 8 mg/L) were recovered and categorized in to two groups (n = 4, n = 1) based on ERIC-PCR and antimicrobial susceptibility patterns. WGS analysis identified tet(X4) variant in three isolates, which belonged to sequence types ST224 (n = 2) and ST10 (n = 1). ResFinder database analysis revealed coexistence of tet(X4) with multiple antibiotic resistance genes including aadA, aph, blaCTX-M-15 and /or blaTEM-1B, floR, cmlA, dfrA, sul and qnrS/mutations in gyrA and parC genes. The tet(X4)-positive E. coli isolates contained the IncX1 and p0111 (strains B52 and R37) or IncX1, IncQ1, IncI1-I(α) and IncFII/IncFIA/IncFIB (strain M55) replicon types according to PlasmidFinder analysis. The tet(X4) gene was successfully mobilized to tigecycline -susceptible recipient E. coli isolates through conjugation assay and demonstrated high stability persisting over 10 consecutive passages in antibiotic-free media in both transconjugants and their donors. This study reports, for the first time in Iran, the emergence of transferrable high-level tigecycline/eravacycline resistance gene tet(X4) in E. coli isolates. Given the public health implications, control measures should be implemented to regulate the use of tetracyclines and potentially phenicols in food animals to prevent emergence and further transmission of such superbugs along the animal- environment -human chain.
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Affiliation(s)
- Mehri Haeili
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
| | - Mahdi Aghajanzadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | | | - Maryam Omrani
- IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Arash Ghodousi
- IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Vita-Salute San Raffaele University, Milan, Italy.
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Gao T, Wang Y, Zhu J, Chen M, Yang K, Yuan F, Liu Z, Liu W, Guo R, Tian H, Li C, Wu Q, Li L, Tian Y, Zhou D. Antibacterial activity of a plant natural poly-phenol against zoonotic Streptococcus suis. Microb Pathog 2025; 205:107655. [PMID: 40355052 DOI: 10.1016/j.micpath.2025.107655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 02/21/2025] [Accepted: 04/29/2025] [Indexed: 05/14/2025]
Abstract
The increasing emergence and dissemination of multi-drugs resistant bacterial pathogens accelerate the desires for novel antimicrobials. Natural products are great resources for the discovery of antimicrobial compound. In this study, pyrogallol was screened from 25 poly-phenols for its antibacterial activity against multi-drugs resistant Streptococcus suis (S. suis), particularly, pyrogallol had synergistic antimicrobial effect with doxycycline, sulfafurazole and clindamycin, respectively. Pyrogallol showed significant inhibitory effects on bacterial biofilm formation, and caused cell wall and cell membrane injury to S. suis. Furthermore, mechanistic studies demonstrated that pyrogallol might interact with peptidoglycan and decreased the expression of virulence and growth-related genes, such as ftsZ, stK, sly, fbps and luxS. In cell model, pyrogallol protected Nptr cells from S. suis-mediated cell damage. Finally, in mouse model, the pyrogallol and antibiotics combination groups with dosage given in the half could be as effective as antibiotics groups. In summary, these results demonstrated the capacity of pyrogallol serving as a candidate for novel antibiotic alternative and antibiotic adjuvant to circumvent the antibiotics resistance and reduced antibiotic consumption.
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Affiliation(s)
- Ting Gao
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Yanjun Wang
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China; State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - JiaJia Zhu
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Mo Chen
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China; College of Animal Science and Technology, Yangtze University, Jingzhou, China
| | - Keli Yang
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Fangyan Yuan
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Zewen Liu
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Wei Liu
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Rui Guo
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Haibin Tian
- Wuhan Fengmeihe Animal Husbandry Technology Co. LTD, Wuhan, China
| | - Chang Li
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Qiong Wu
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China
| | - Lu Li
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Yongxiang Tian
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China.
| | - Danna Zhou
- Key Laboratory of Prevention and Control Agents for Animal Bacteriosis (Ministry of Agriculture and Rural Affairs), Hubei Provincial Key Laboratory of Animal Pathogenic Microbiology, Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan, China.
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6
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Tang H, Liu Z, Hu B, Zhu L. Hierarchical activation of resistance genes under tetracyclines selective pressure in complex microbial community. JOURNAL OF HAZARDOUS MATERIALS 2025; 493:138399. [PMID: 40300515 DOI: 10.1016/j.jhazmat.2025.138399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 04/21/2025] [Accepted: 04/22/2025] [Indexed: 05/01/2025]
Abstract
The pervasive use of antibiotics exerts selective pressure in both natural and anthropogenic environments, driving the propagation and evolution of antibiotic resistance genes (ARGs) in microbial communities. Understanding the succession of resistome under varying antibiotic stresses is crucial for mitigating the spread of ARGs. This study investigates the succession of resistome under exposure to four structurally different tetracyclines (TC) across concentrations ranging from environmental to clinical levels. A clear hierarchical activation of ARGs was observed, starting with the upregulation of multidrug and TC-specific efflux pump genes, followed by those involved in TC inactivation and ribosomal protection. By identifying the specific thresholds of transcriptional onset times and critical TC concentration ranges that triggered ARG abundance increases, it was found that all ARGs as a whole did not significantly increase when TC concentrations were maintained below 10-5 of the initial minimum inhibitory concentration (MIC0) within 2 h. Similarly, high-risk TC resistance genes do not proliferate when TC concentrations were kept below 10-3 × MIC0 within 24 h. These findings provide quantifiable benchmarks for concentration-time thresholds that can inform the establishment of environmental discharge limits and guide the implementation of targeted treatment technologies to mitigate ARG dissemination.
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Affiliation(s)
- Huiming Tang
- College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Zhejiang University, Hangzhou 310058, China
| | - Zishu Liu
- College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China
| | - Baolan Hu
- College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China
| | - Lizhong Zhu
- College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Soil Pollution Control and Safety, Zhejiang University, Hangzhou 310058, China.
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7
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Kerek Á, Román I, Szabó Á, Kovács D, Kardos G, Kovács L, Jerzsele Á. Antibiotic resistance genes in Escherichia coli - literature review. Crit Rev Microbiol 2025:1-35. [PMID: 40249005 DOI: 10.1080/1040841x.2025.2492156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 03/25/2025] [Accepted: 04/07/2025] [Indexed: 04/19/2025]
Abstract
Antimicrobial resistance threatens humans and animals worldwide and is recognized as one of the leading global public health issues. Escherichia coli (E. coli) has an unquestionable role in carrying and transmitting antibiotic resistance genes (ARGs), which in many cases are encoded on plasmids or phage, thus creating the potential for horizontal gene transfer. In this literature review, the authors summarize the major antibiotic resistance genes occurring in E. coli bacteria, through the major antibiotic classes. The aim was not only listing the resistance genes against the clinically relevant antibiotics, used in the treatment of E. coli infections, but also to cover the entire resistance gene carriage in E. coli, providing a more complete picture. We started with the long-standing antibiotic groups (beta-lactams, aminoglycosides, tetracyclines, sulfonamides and diaminopyrimidines), then moved toward the newer groups (phenicols, peptides, fluoroquinolones, nitrofurans and nitroimidazoles), and in every group we summarized the resistance genes grouped by the mechanism of their action (enzymatic inactivation, antibiotic efflux, reduced permeability, etc.). We observed that the frequency of antibiotic resistance mechanisms changes in the different groups.
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Affiliation(s)
- Ádám Kerek
- Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, Budapest, Hungary
- National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, Budapest, Hungary
| | - István Román
- Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, Budapest, Hungary
| | - Ábel Szabó
- Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, Budapest, Hungary
| | - Dóra Kovács
- National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, Budapest, Hungary
| | - Gábor Kardos
- One Health Institute, University of Debrecen, Debrecen, Hungary
- National Public Health Center, Budapest, Hungary
- Department of Gerontology, Faculty of Health Sciences, University of Debrecen, Nyíregyháza, Hungary
| | - László Kovács
- National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, Budapest, Hungary
- Department of Animal Hygiene, Herd Health and Mobile Clinic, University of Veterinary Medicine, Budapest, Hungary
| | - Ákos Jerzsele
- Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest, Budapest, Hungary
- National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest, Budapest, Hungary
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Sun H, Liang G, Chen B, Jia J, Jing H. A novel ZnO/Fe 3+-doped Bi 2WO 6 photocatalyst with triple synergistic effect for solar-driven tetracycline degradation. RSC Adv 2025; 15:12689-12697. [PMID: 40264883 PMCID: PMC12012601 DOI: 10.1039/d5ra01899d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Accepted: 04/08/2025] [Indexed: 04/24/2025] Open
Abstract
To address the limited visible-light absorption and rapid charge recombination of Bi2WO6 photocatalysts, this work constructs a Z-scheme ZnO/Fe3+-doped Bi2WO6 heterojunction via a hydrothermal-calcination method. The Fe3+ doping induces the formation of oxygen vacancies and optimizes the band structure, which cooperates with the interface reconstruction of ZnO to expand the light absorption to 480 nm. The hierarchical pore structure simultaneously enhances the mass transfer efficiency, and finally realizes the efficient degradation of tetracycline under visible light (the removal rate is 95.5% in 60 minutes, and the rate is 2.28 times higher than that of the pure phase) and the stable cycle performance is good. Mechanistic studies demonstrate that Z-scheme charge transfer driven by an interfacial built-in electric field ensures effective carrier separation, with photogenerated holes (h+) as key reactive species. The proposed "defect-heterojunction-interface trinity" strategy establishes a new design scheme for bismuth-based Z-scheme photocatalysts.
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Affiliation(s)
- Hui Sun
- School of Chemistry and Chemical Engineering, North University of China Taiyuan 030051 P. R. China
| | - Gaoyang Liang
- School of Chemistry and Chemical Engineering, North University of China Taiyuan 030051 P. R. China
| | - Bingge Chen
- School of Chemistry and Chemical Engineering, North University of China Taiyuan 030051 P. R. China
| | - Jingqi Jia
- School of Chemistry and Chemical Engineering, North University of China Taiyuan 030051 P. R. China
| | - Hongxia Jing
- School of Chemistry and Chemical Engineering, North University of China Taiyuan 030051 P. R. China
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9
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Bisaccia M, Berini F, Marinelli F, Binda E. Emerging Trends in Antimicrobial Resistance in Polar Aquatic Ecosystems. Antibiotics (Basel) 2025; 14:394. [PMID: 40298543 PMCID: PMC12024378 DOI: 10.3390/antibiotics14040394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/01/2025] [Accepted: 04/04/2025] [Indexed: 04/30/2025] Open
Abstract
The global spread of antimicrobial resistance (AMR) threatens to plummet society back to the pre-antibiotic era through a resurgence of common everyday infections' morbidity. Thus, studies investigating antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in urban, agricultural, and clinical settings, as well as in extreme environments, have become increasingly relevant in the One Health perspective. Since the Antarctic and Arctic regions are considered amongst the few remaining pristine environments on Earth, the characterization of their native resistome appears to be of the utmost importance to understand whether and how it is evolving as a result of anthropogenic activities and climate change. In the present review, we report on the phenotypic (e.g., disk diffusion test) and genotypic (e.g., PCR, metagenomics) approaches used to study AMR in the aquatic environment of polar regions, as water represents one of AMR main dissemination routes in nature. Their advantages and limits are described, and the emerging trends resulting from the analysis of ARB and ARGs diffusion in polar waters discussed. The resistome detected in these extreme environments appears to be mostly comparable to those from more anthropized areas, with the predominance of tetracycline, β-lactam, and sulfonamide resistance (and related ARGs). Indeed, AMR is, in all cases, more consistently highlighted in sites impacted by human and wildlife activities with respect to more pristine ones. Surprisingly, aminoglycoside and fluroquinolone determinants seem to have an even higher incidence in the Antarctic and Arctic aquatic environment compared to that from other areas of the world, corroborating the need for a more thorough AMR surveillance in these regions.
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Affiliation(s)
- Melissa Bisaccia
- Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy; (M.B.); (F.B.); (E.B.)
| | - Francesca Berini
- Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy; (M.B.); (F.B.); (E.B.)
- Climate Change Research Center (CCRC), University of Insubria, 22100 Como, Italy
| | - Flavia Marinelli
- Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy; (M.B.); (F.B.); (E.B.)
- Climate Change Research Center (CCRC), University of Insubria, 22100 Como, Italy
| | - Elisa Binda
- Department of Biotechnology and Life Sciences (DBSV), University of Insubria, 21100 Varese, Italy; (M.B.); (F.B.); (E.B.)
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Sun Y, Luo Y, Wang H, He Y, Wang R, Lu M, Xu D. Electrochemical detection of tetracycline by zinc oxide modified with molecularly-imprinted polymers. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2025; 17:3027-3035. [PMID: 40165646 DOI: 10.1039/d5ay00270b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
An efficient electrochemical molecularly imprinted sensor for the detection of tetracycline (TC) was prepared using ZnO/MIP. ZnO nanomaterials with large surface area improved the electrochemical detection performance and also increased the binding sites of the TC molecularly imprinted polymeric membrane. The TC molecularly imprinted polymeric membrane with pyrrole as the functional monomer specifically binds to TC and thus detects TC in the sample. In this study, the electrochemical performance of ZnO/MIP was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Under the optimal conditions, ZnO/MIP showed a wide detection range. The detection range was 0.1-100 nM, and the detection limit was 0.02 nM with R2 reaching 0.9974. ZnO/MIP has good selectivity, stability, and reproducibility. The recovery of tetracycline in milk was 97-112%.
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Affiliation(s)
- Yiwei Sun
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Yuting Luo
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Haoxiang Wang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Yuyang He
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Ruoyu Wang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Mengqi Lu
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
| | - Dongpo Xu
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, PR China.
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11
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Strutt R, Jusková P, Berlanda SF, Krämer SD, Dittrich PS. Engineering a Biohybrid System to Link Antibiotic Efficacy to Membrane Depth in Bacterial Infections. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2412399. [PMID: 40143780 DOI: 10.1002/smll.202412399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Indexed: 03/28/2025]
Abstract
Treating bacterial infections is dependent upon their site within a biological system, where the cumulative role of membrane transport is challenging to resolve. In this work, a cultivation method based on droplet interface bilayers (DIBs) is established. The architecture of infections in both cellular and tissue contexts is crafted where individual droplets serve as artificial cells infected by intracellular bacteria, or as interconnected units in a tissue-like structure. Through spatio-temporal control over droplets, addition, withdrawal, and sequential antibiotic gradients are tailored acting upon living bacteria. With droplet networks mimicking tissues, it is showed that the treatment response is dependent on the number of the cell-like barriers, corresponding to the number of membranes from an antibiotic source, here described as the membrane depth. Through mathematical modelling a correlation is revealed between the membrane depth of each bacterial population, the antibiotic distribution and thus the treatment efficacy. Ultimately, this approach holds promise as an in vitro bioassay for understanding the response of intracellular bacteria to antibiotics, developing new antibiotics, designing biologically inspired materials, and underpinning emerging bioprinting approaches.
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Affiliation(s)
- Robert Strutt
- Department of Biosystems Science and Engineering, ETH Zürich, Schanzenstrasse 44, Basel, 4056, Switzerland
| | - Petra Jusková
- Department of Biosystems Science and Engineering, ETH Zürich, Schanzenstrasse 44, Basel, 4056, Switzerland
| | - Simon F Berlanda
- Department of Biosystems Science and Engineering, ETH Zürich, Schanzenstrasse 44, Basel, 4056, Switzerland
| | - Stefanie D Krämer
- Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 4, Zürich, 8093, Switzerland
| | - Petra S Dittrich
- Department of Biosystems Science and Engineering, ETH Zürich, Schanzenstrasse 44, Basel, 4056, Switzerland
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12
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Tantalo LC, Luetkemeyer AF, Lieberman NAP, Nunley BE, Avendaño C, Greninger AL, Celum C, Giacani L. In Vitro Exposure of Treponema pallidum to Subbactericidal Doxycycline Did Not Induce Resistance: Implications for Doxycycline Postexposure Prophylaxis. J Infect Dis 2025; 231:729-733. [PMID: 39067061 PMCID: PMC11911782 DOI: 10.1093/infdis/jiae381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/22/2024] [Accepted: 07/25/2024] [Indexed: 07/30/2024] Open
Abstract
Doxycycline postexposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistant Treponema pallidum strains. To assess whether resistance to doxycycline could be induced in this pathogen, we exposed the SS14 strain in vitro, both intermittently and continuously, to a subbactericidal doxycycline concentration that still exerts antibiotic pressure. During and after each exposure experiment, we assessed the doxycycline minimal inhibitory concentration in test and control treponemes and performed whole-genome sequencing, concluding that no resistance developed. This work suggests that doxycycline-resistant T. pallidum is not an immediate threat for doxy-PEP implementation.
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Affiliation(s)
- Lauren C Tantalo
- Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
| | - Anne F Luetkemeyer
- Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Nicole A P Lieberman
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - B Ethan Nunley
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Carlos Avendaño
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Alexander L Greninger
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Connie Celum
- Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
| | - Lorenzo Giacani
- Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA
- Department of Global Health, University of Washington, Seattle, Washington, USA
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13
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Valencia EY, Nunes VA, Chambergo FS, Spira B. ADP-MoA-Pa: a platform for screening antibiotic activity and their mechanism of action in Pseudomonas aeruginosa. J Appl Microbiol 2025; 136:lxaf058. [PMID: 40053502 DOI: 10.1093/jambio/lxaf058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/26/2025] [Accepted: 03/06/2025] [Indexed: 03/09/2025]
Abstract
AIMS The emergence of multidrug-resistant bacteria poses a significant threat to global public health. To address this crisis, there is an urgent need to identify and characterize novel antibacterial molecules. This study aimed to develop the ADP-MoA-Pa platform to facilitate the discovery of new antibiotics and provide preliminary insights into their mechanisms of action (MoA). METHODS AND RESULTS The ADP-MoA-Pa platform enables the simultaneous visualization of antibiotic activity (growth inhibition) alongside one of three classic MoA in Pseudomonas aeruginosa: DNA damage/inhibition of DNA replication, protein synthesis inhibition, or cell wall damage. To construct the platform, the promoter regions of recA, ampC, and armZ of P. aeruginosa PA14 strain were each amplified and fused to a promoterless luxCDABE operon in vector pUC18T-mini-Tn7T-lux-Gm. The constructs were electrotransformed into strain PA14 where they integrated in the chromosome. Each promoter fusion was activated by the expected antibiotics on plates and in liquid media, thereby demonstrating proof of concept. The armZ::luxCDABE fusion responded to protein synthesis inhibitors such as macrolides, chloramphenicol, tetracyclines, and aminoglycosides. The ampC::luxCDABE fusion was induced by β-lactams, while the recA::luxCDABE fusion was activated by quinolones and nitrofurantoin. Interestingly, under some conditions, ciprofloxacin also activated ampC and armZ, though to a lesser extent. CONCLUSIONS The ADP-MoA-Pa platform is a low-cost, readily implementable tool with significant potential for high-throughput screening of antimicrobials. It offers a promising avenue for identifying and characterizing novel antibiotics against P. aeruginosa and other bacterial species, contributing to the global effort to combat multidrug-resistant pathogens.
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Affiliation(s)
- Estela Ynés Valencia
- Departamento de Microbiologia, Universidade de São Paulo, Av. Prof. Lineu Prestes 1374, São Paulo, 05508-000, Brazil
- XYZ Molecular Target LTDA, Av. Prof. Lineu Prestes 1374, São Paulo, 05508-000, Brazil
| | - Viviane Abreu Nunes
- Escola de Artes, Ciências e Humanidades, Av. Arlindo Bettio 1000, Universidade de São Paulo, São Paulo, 3828-000, Brazil
| | - Felipe S Chambergo
- Escola de Artes, Ciências e Humanidades, Av. Arlindo Bettio 1000, Universidade de São Paulo, São Paulo, 3828-000, Brazil
| | - Beny Spira
- Departamento de Microbiologia, Universidade de São Paulo, Av. Prof. Lineu Prestes 1374, São Paulo, 05508-000, Brazil
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14
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Parmar M, Das A, Vala DP, Bhalodiya SS, Patel CD, Balachandran S, Kandukuri NK, Kashyap S, Khan AN, González-Bakker A, Arumugam MK, Padrón JM, Nandi A, Banerjee S, Patel HM. QSAR, Antimicrobial, and Antiproliferative Study of ( R/ S)-2-Thioxo-3,4-dihydropyrimidine-5-carboxanilides. ACS OMEGA 2025; 10:7013-7026. [PMID: 40028097 PMCID: PMC11866182 DOI: 10.1021/acsomega.4c09899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 03/05/2025]
Abstract
Owing to the significant contribution of three-dimensional (3D) field-based QSAR toward hit optimization and accurately predicting the activities of small molecules, herein, the 3D-QSAR, in vitro antimicrobial, molecular docking, and pharmacophore modeling studies of all the isolated (R/S)-2-thioxo-DHPM-5-carboxanilides exhibiting antimicrobial activity were carried out. The screening process was performed using 46 compounds, and the best-scoring model with the top statistical values was considered for bacterial and fungal targets Bacillus subtilis and Candida albicans. As a result of 3D-QSAR analysis, compound 4v-(S)- and 4v-(R)-isomers were found to be more potent compared to the standard drugs tetracycline and fluconazole, respectively. Furthermore, the enantiomerically pure isomers 4q, 4d', 4n, 4f', 4v, 4q', 4c, and 4p' were found to be more potent than tetracycline and fluconazole to inhibit the bacterial and fungal growth against B. subtilis, Salinivibrio proteolyticus, C. albicans, and Aspergillus niger, respectively. Molecular docking analysis shows that with the glide score of -10.261 kcal/mol, 4v-(R)-isomer was found to be more potent against the fungal target C. albicans and may target the 14-α demethylase than fluconazole. Furthermore, all compounds' antiproliferative activity results showed that 4o' exhibited GI50 values between 8.8 and 34 μM against six solid tumor cell lines. Following the greater potential of 4o' toward the HeLa cell line, its kinetics study and live cell imaging were carried out. These outcomes highlight the acceptance and safety as well as the potential of compounds as effective antiproliferative and antifungal agents.
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Affiliation(s)
- Mehul
P. Parmar
- Department
of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India
| | - Anwesha Das
- Department
of Pharmacy, Sanaka Educational Trust Group
of Institutions (SETGOI), Malandighi, Durgapur, West Bengal 713212, India
| | - Disha P. Vala
- Department
of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India
| | - Savan S. Bhalodiya
- Department
of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India
| | - Chirag D. Patel
- Department
of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India
| | - Shana Balachandran
- Cancer
Biology Lab, Center for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu 600119, India
| | - Nagesh Kumar Kandukuri
- YMC
Application Lab, Plot
No. 78/A/6, Phase VI, Industrial Park Jeedimetla,
Gajularamaram Village, Quthbullapur, Medchal, Hyderabad, Telangana 500055, India
| | - Shreya Kashyap
- Division
of Cancer Research, School of Medicine, University of Dundee, Dundee DD1 9SY, U.K.
| | - Adam N. Khan
- BioLab,
Instituto
Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez
2, La Laguna 38206, Spain
| | - Aday González-Bakker
- BioLab,
Instituto
Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez
2, La Laguna 38206, Spain
| | - Madan Kumar Arumugam
- Cancer
Biology Lab, Center for Molecular and Nanomedical Sciences, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu 600119, India
| | - José M. Padrón
- BioLab,
Instituto
Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez
2, La Laguna 38206, Spain
| | - Arijit Nandi
- Department
of Pharmacy, Sanaka Educational Trust Group
of Institutions (SETGOI), Malandighi, Durgapur, West Bengal 713212, India
- Institute
for Molecular Bioscience, The University
of Queensland, 306 Carmody RoadSt Lucia Qld, Brisbane 4072, Australia
| | - Sourav Banerjee
- Division
of Cancer Research, School of Medicine, University of Dundee, Dundee DD1 9SY, U.K.
| | - Hitendra M. Patel
- Department
of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat 388120, India
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15
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Shao K, Yang Y, Gong X, Chen K, Liao Z, Ojha SC. Staphylococcal Drug Resistance: Mechanisms, Therapies, and Nanoparticle Interventions. Infect Drug Resist 2025; 18:1007-1033. [PMID: 39990781 PMCID: PMC11847421 DOI: 10.2147/idr.s510024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 02/06/2025] [Indexed: 02/25/2025] Open
Abstract
The increasing incidence of antibiotic resistance in Staphylococcus aureus (S. aureus) poses a substantial threat to global public health. In recent decades, the evolution of bacteria and the misuse of antibiotics have led to a progressive development in drug resistance of S. aureus, resulting in a worldwide rise in methicillin-resistant S. aureus (MRSA) infection rates. Understanding the molecular mechanisms underlying staphylococcal drug resistance, the treatments for staphylococcal infections, and the efficacy of nanomaterials in addressing multi-drug resistance is crucial. This review explores the resistance mechanisms, which include limiting drug uptake, target modification, drug inactivation through the production of degrading enzymes, and active efflux of drugs. It also examines the current therapeutic strategies, such as antibiotic combination therapy, phage therapy, monoclonal antibody therapy, and nanoparticle therapy, with a particular emphasis on the role of silver-based nanomaterials. Nanoparticles possess the ability to overcome multi-drug resistance, offering a novel avenue for the management of drug-resistant bacteria. The nanomaterials have demonstrated potent antibacterial activity against S. aureus through various mechanisms, including cell membrane disruption, generation of reactive oxygen species (ROS), and inhibition of essential cellular processes. It also highlights the need for further research to optimize nanoparticle design, enhance their antibacterial potency, and ensure their biocompatibility and biodegradability. The review ultimately concludes by emphasizing the importance of a multifaceted approach to treatment, including the development of new antibiotics, investment in stewardship programs to prevent antibiotic misuse, and the exploration of natural compounds and bacteriocins as potential antimicrobial agents.
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Affiliation(s)
- Kunyu Shao
- School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China
| | - Yuxun Yang
- School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China
| | - Xuankai Gong
- School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China
| | - Ke Chen
- School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China
- Department of Infectious Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China
| | - Zixiang Liao
- School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China
| | - Suvash Chandra Ojha
- Department of Infectious Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China
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16
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Blake KS, Xue YP, Gillespie VJ, Fishbein SRS, Tolia NH, Wencewicz TA, Dantas G. The tetracycline resistome is shaped by selection for specific resistance mechanisms by each antibiotic generation. Nat Commun 2025; 16:1452. [PMID: 39920134 PMCID: PMC11806011 DOI: 10.1038/s41467-025-56425-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 01/14/2025] [Indexed: 02/09/2025] Open
Abstract
The history of clinical resistance to tetracycline antibiotics is characterized by cycles whereby the deployment of a new generation of drug molecules is quickly followed by the discovery of a new mechanism of resistance. This suggests mechanism-specific selection by each tetracycline generation; however, the evolutionary dynamics of this remain unclear. Here, we evaluate 24 recombinant Escherichia coli strains expressing tetracycline resistance genes from each mechanism (efflux pumps, ribosomal protection proteins, and enzymatic inactivation) in the context of each tetracycline generation. We employ a high-throughput barcode sequencing protocol that can discriminate between strains in mixed culture and quantify their relative abundances. We find that each mechanism is preferentially selected for by specific antibiotic generations, leading to their expansion. Remarkably, the minimum inhibitory concentration associated with individual genes is secondary to resistance mechanism for inter-mechanism relative fitness, but it does explain intra-mechanism relative fitness. These patterns match the history of clinical deployment of tetracycline drugs and resistance discovery in pathogens.
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Affiliation(s)
- Kevin S Blake
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Yao-Peng Xue
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
| | - Vincent J Gillespie
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
| | - Skye R S Fishbein
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Niraj H Tolia
- Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
| | - Timothy A Wencewicz
- Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA.
| | - Gautam Dantas
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
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17
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Li X, Zhao J, Liu X, Song Z, Xu W, Li Z. Probing the interaction mechanism of tigecycline with γ-globulin and hemoglobin in the absence and presence of amikacin. Int J Biol Macromol 2025; 291:139109. [PMID: 39722387 DOI: 10.1016/j.ijbiomac.2024.139109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/02/2024] [Accepted: 12/21/2024] [Indexed: 12/28/2024]
Abstract
The interaction mechanism of tigecycline with γ-globulin and hemoglobin in the absence and presence of amikacin was investigated through multipectral, molecular docking and molecular dynamics simulation. The results show that tigecycline and γ-globulin/hemoglobin forms a ground state complex without or with amikacin. The presence of amikacin slightly increases the binding constant of tigecycline to γ-globulin/hemoglobin, but all are of moderate binding affinity, at 104 L mol-1. The equilibrium fraction of unbound tigecycline fu is >90 %, but the presence of amikacin reduces the free concentration of tigecycline in γ-globulin and hemoglobin. Whether amikacin is present or not, the interaction between tigecycline and γ-globulin/hemoglobin is a synergistic interaction driven by enthalpy and entropy. Non-covalent forces are primarily hydrophobic interactions, but also include electrostatic forces and hydrogen bonds. In the presence of amikacin, the effect of tigecycline on the skeleton structure of γ-globulin/hemoglobin is more significant. The effect of tigecycline and/or amikacin on the secondary structure of γ-globulin/hemoglobin is not significant, while the secondary structure changes in different systems are not the same. Molecular docking shows that γ-globulin/hemoglobin-tigecycline (first)-amikacin ternary system is the most stable. Molecular dynamics simulation explores the stability and dynamic behavior of γ-globulin/hemoglobin-tigecycline complex without or with amikacin.
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Affiliation(s)
- Xiangrong Li
- Department of Medical Chemistry, Xinxiang Engineering Technology Research Center of Functional Medical Nanomaterials, Key Laboratory of Medical Molecular Probes, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China.
| | - Jingjing Zhao
- Department of Medical Chemistry, Xinxiang Engineering Technology Research Center of Functional Medical Nanomaterials, Key Laboratory of Medical Molecular Probes, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China; Clinical Pharmacy Room, Pharmacy Department, Xinmi Hospital of Traditional Chinese Medicine, Xinmi, Henan 452370, PR China
| | - Xianfei Liu
- Department of Medical Chemistry, Xinxiang Engineering Technology Research Center of Functional Medical Nanomaterials, Key Laboratory of Medical Molecular Probes, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China; School of Life Science, Ludong University, Yantai, Shandong 264025, PR China
| | - Zhizhi Song
- Grade 2020, Clinical Medicine, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China
| | - Wanqing Xu
- Grade 2022, Clinical Medicine, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China
| | - Zheng Li
- Grade 2022, Clinical Medicine, School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China
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18
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Chappell L, Peguero R, Conner WR, Fowler S, Cooper B, Pfarr K, Hoerauf A, Lustigman S, Sakanari J, Sullivan W. Fexinidazole and Corallopyronin A target Wolbachia-infected sheath cells present in filarial nematodes. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.23.634442. [PMID: 39896488 PMCID: PMC11785234 DOI: 10.1101/2025.01.23.634442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
The discovery of the endosymbiotic bacteria Wolbachia as an obligate symbiont of filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab and clinical studies have yielded promising results, recent animal studies reveal that Wolbachia levels may rebound following treatment with suboptimal doses of the antibiotic rifampicin. Previous work showed that a likely source of the bacterial rebound in females were dense clusters of Wolbachia in ovarian tissue. The number, size, and density of these Wolbachia clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the Wolbachia clusters in Brugia pahangi (wBp) and identify drugs that also target them. We have evidence that the Wolbachia clusters originate from newly formed sheath cells adjacent to the ovarian Distal Tip Cells. The dramatically enlarged volume of an infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered Wolbachia present within the sheath cells exhibit a distinct morphology and form direct connections with the oocyte membrane and possibly the cytoplasm. This includes membrane-based channels providing a connection between Wolbachia-infected sheath cells and oocytes. We also determined that the Wolbachia within the sheath cells are either quiescent or replicating at a very low rate. Screens of known antibiotics and other drugs revealed that two drugs, Fexinidazole and Corallopyronin A, significantly reduced the number of clustered Wolbachia located within the sheath cells.
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Affiliation(s)
- Laura Chappell
- Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA
| | - Ricardo Peguero
- Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA
| | - William R Conner
- Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA
| | - Sommer Fowler
- Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA
| | - Brandon Cooper
- Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA
| | - Kenneth Pfarr
- Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
| | - Achim Hoerauf
- Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Germany
- German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
| | - Sara Lustigman
- Molecular Parasitology, New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA
| | - Judy Sakanari
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA
| | - William Sullivan
- Department of Molecular, Cellular and Developmental Biology University of California, Santa Cruz, CA 95064, USA
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19
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Xie J, Islam S, Wang L, Zheng X, Xu M, Su X, Huang S, Suits L, Yang G, Eswara P, Cai J, Ming LJ. A tale of two old drugs tetracycline and salicylic acid with new perspectives-Coordination chemistry of their Co(II) and Ni(II) complexes, redox activity of Cu(II) complex, and molecular interactions. J Inorg Biochem 2025; 262:112757. [PMID: 39423693 DOI: 10.1016/j.jinorgbio.2024.112757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 09/13/2024] [Accepted: 10/06/2024] [Indexed: 10/21/2024]
Abstract
Extensive use of the broad-spectrum tetracycline antibiotics (TCs) has resulted their wide spread in the environment and drive new microecological balances, including the infamous antibiotic resistance. TCs require metal ions for their antibiotic activity and resistance via interactions with ribosome and tetracycline repressor TetR, respectively, at specific metal-binding sites. Moreover, the Lewis-acidic metal center(s) in metallo-TCs can interact with Lewis-basic moieties of many bioactive secondary metabolites, which in turn may alter their associated chemical equilibria and biological activities. Thus, it is ultimately important to reveal detailed coordination chemistry of metallo-TC complexes. Herein, we report (a) conclusive specific Co2+, Ni2+, and Cu2+-binding of TC revealed by paramagnetic 1H NMR, showing different conformations of the coordination and different metal-binding sites in solution and solid state, (b) significant metal-mediated activity of Cu-TC toward catechol oxidation with different mechanisms by air and H2O2 (i.e., mono- and di-nuclear pathways, respectively), (c) interactions of metallo-TCs with bioactive salicylic acid and its precursor benzoic acid, and (d) noticeable change of TC antibiotic activity by metal and salicylic acid. The results imply that TCs may play broad and versatile roles in maintaining certain equilibria in microecological environments in addition to their well-established antibiotic activity. We hope the results may foster further exploration of previously unknown metal-mediated activities of metallo-TC complexes and other metalloantibiotics.
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Affiliation(s)
- Jinhua Xie
- College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, PR China
| | - Shahedul Islam
- Department of Chemistry, University of South Florida, Tampa, FL 33620-5250, USA
| | - Le Wang
- College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, PR China
| | - Xiaojing Zheng
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, PR China
| | - Mengsheng Xu
- College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, PR China
| | - Xiqi Su
- College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, PR China
| | - Shaohua Huang
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, PR China
| | - Logan Suits
- Department of Molecular Biosciences, ISA6207, University of South Florida, Tampa, FL 33620, USA
| | - Guang Yang
- Department of Chemistry, University of South Florida, Tampa, FL 33620-5250, USA
| | - Prahathees Eswara
- Department of Molecular Biosciences, ISA6207, University of South Florida, Tampa, FL 33620, USA
| | - Jianfeng Cai
- Department of Chemistry, University of South Florida, Tampa, FL 33620-5250, USA
| | - Li-June Ming
- Department of Chemistry, University of South Florida, Tampa, FL 33620-5250, USA; Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, PR China.
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20
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Wang Y, Luo Y, Tan Z, Lu X, Zhao L, Usman Ghani M, Sun W, Ren Y. Biotransformation of chloramphenicol by enriched bacterial consortia and the newly isolated bacterial strain Bordetella sp. C3: Detoxifying biotransformation pathway and its potential application in agriculture. BIORESOURCE TECHNOLOGY 2025; 415:131713. [PMID: 39477164 DOI: 10.1016/j.biortech.2024.131713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/08/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024]
Abstract
Limited sources of consortia/pure cultures that degrade chloramphenicol (CAP) and the incomplete biodegradation profiles of CAP hinder the remediation of CAP pollution. In this study, two CAP-degrading consortia (designated as CM and PM) were obtained after long-term acclimation, and Alcaligenaceae and Enterobacteriaceae enriched in CM and PM, respectively. Notably, Bordetella sp. C3, a new isolate belonging to the family Alcaligenaceae, was isolated from CM and capable of degrading 85.7 % 10 mg/L CAP at 30 ℃ and pH 7 in 10 d. The biotransformation of CAP by Bordetella sp. C3 was proposed as a detoxification process, including a novel initial degradation pathway: dechlorination of CAP into AP. Strain C3 can also function as a plant growth-promoting bacterium that solubilizes inorganic phosphate and produces siderophores and indole-3-acetic acid (IAA). This study expands our knowledge of the migration and transformation pathways of CAP and microbial community profiles during acclimatization.
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Affiliation(s)
- Yuanliang Wang
- College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Yujiang Luo
- College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China; National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou 510650, China
| | - Zewen Tan
- National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou 510650, China.
| | - Xingjun Lu
- School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua 418000, China
| | - Li Zhao
- China Water Resources Pearl River Planning Surveying & Designing Co., Ltd., Guangzhou 510610, China
| | - Muhammad Usman Ghani
- National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou 510650, China; Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, 38040, Pakistan
| | - Weimin Sun
- National-Regional Joint Engineering Research Center for Soil Pollution Control and Remediation in South China, Guangdong Key Laboratory of Integrated Agro-environmental Pollution Control and Management, Institute of Eco-environmental and Soil Sciences, Guangdong Academy of Sciences, Guangzhou 510650, China
| | - Youhua Ren
- College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China.
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21
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Khaled O, Ryad L, Eissa F. Determination of tetracycline residues in potatoes and soil by LC-MS/MS: Method development, validation, and risk assessment. Food Chem 2024; 461:140841. [PMID: 39146681 DOI: 10.1016/j.foodchem.2024.140841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/31/2024] [Accepted: 08/09/2024] [Indexed: 08/17/2024]
Abstract
A method utilizing liquid-liquid extraction (LLE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated according to the Commission Implementing Regulation (CIR) EU 2021/808 for quantifying four tetracyclines (TCs) in potatoes and soil. The method demonstrated recovery values ranging from 70 to 121% and precision (repeatability and within-laboratory reproducibility), with coefficient of variation (CV) values below 18% for all TCs in both matrices. The limits of quantification (LOQs) for the TCs ranged from 0.90 to 1.87 μg/kg in potatoes and from 0.68 to 1.25 μg/kg in soil. The decision limit (CCα) and detection capability (CCβ) ranged from 10.4 to 12.3 μg/kg and 11.9 to 14.3 μg/kg, respectively. Analysis of 538 potato and soil samples from Egyptian farms revealed a 13.2% occurrence of TC residues, with a higher frequency in soil (19.33%) than in potatoes (7.06%). Target hazard quotient (THQ) values indicated that TC residues in potatoes do not pose a health risk to Egyptian consumers.
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Affiliation(s)
- Omar Khaled
- Agriculture Research Centre, Central Laboratory of Residue Analysis of Pesticides and Heavy Metals in Foods, Ministry of Agriculture, Giza 12311, Egypt
| | - Lamia Ryad
- Agriculture Research Centre, Central Laboratory of Residue Analysis of Pesticides and Heavy Metals in Foods, Ministry of Agriculture, Giza 12311, Egypt
| | - Fawzy Eissa
- Environment and Bio-Agriculture Department, Faculty of Agriculture, Al-Azhar University, 11884, Nasr City, Cairo, Egypt.
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22
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Eichberg C, Leiß A, Stothut M, Bernheine J, Jurczyk K, Paulus L, Thiele-Bruhn S, Thomas FM, Donath TW. Tetracycline but not sulfamethazine inhibits early root growth of wild grassland species, while seed germination is hardly affected by either antibiotic. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 363:125178. [PMID: 39447628 DOI: 10.1016/j.envpol.2024.125178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 09/20/2024] [Accepted: 10/21/2024] [Indexed: 10/26/2024]
Abstract
Seed germination and early growth of grassland species might be influenced by veterinary antibiotics that are extensively released into agricultural habitats. Therefore, we tested impacts of the commonly used antibiotics tetracycline and sulfamethazine, single and in mixture, on seed germination and seedling root growth of six typical species of temperate European grasslands (Carum carvi, Centaurea jacea, Galium mollugo, Plantago lanceolata, Silene latifolia, Dactylis glomerata). In standardised germination experiments, we assessed three germination variables (germination percentage, mean germination time, synchrony of germination) and one post-germination variable (seedling root length) under different environmentally realistic antibiotic concentrations (0.1, 1, 10 mg l-1 and a water control). While the germination variables were only irregularly and weakly affected by both antibiotics, seedling root length was strongly reduced by tetracycline, but not by sulfamethazine. Among the test species, D. glomerata was most sensitive to tetracycline with the average root length reduced up to 81 % in the 10 mg l-1 treatment. Its germination behaviour, however, was almost insensitive to the two antibiotics. Mixture effects were only shown in relation to the germination of single species, where the binary mixture produced effects but not the two single antibiotics or, conversely, effects of single antibiotics were lost in the mixture. These findings highlight the potential threat of plant regeneration from seed by veterinary antibiotics, particularly affecting early root growth and potentially influencing plant population growth in natural habitats.
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Affiliation(s)
- Carsten Eichberg
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany.
| | - Angela Leiß
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Manuel Stothut
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Jan Bernheine
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Kim Jurczyk
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Lena Paulus
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Sören Thiele-Bruhn
- Soil Science, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Frank M Thomas
- Geobotany, Spatial and Environmental Sciences, Trier University, Behringstraße 21, 54296, Trier, Germany
| | - Tobias W Donath
- Department of Landscape Ecology, Institute for Natural Resource Conservation, Kiel University, Olshausenstraße 75, 24118, Kiel, Germany
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23
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Carneiro RF, Tabosa PAS, Cândido JGS, Menezes VPP, Rocha Júnior PAV, Andrade AL, Vasconcelos MA, Teixeira EH, Nagano CS, Sampaio AH. Toward Enhanced Antibiotic Efficacy: Exploring the Synergistic Potential of Marine-Derived Lectins Against Human Pathogenic Bacteria. AN ACAD BRAS CIENC 2024; 96:e20240072. [PMID: 39661826 DOI: 10.1590/0001-3765202420240072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 07/15/2024] [Indexed: 12/13/2024] Open
Abstract
This study aimed to assess the combined antibacterial effect of lectins and antibiotics on S. aureus ATCC 25923, multidrug-resistant E. coli ATCC 11303 and S. aureus ATCC 700698. Using the checkerboard assay, we evaluated the antibacterial effects of eight lectins isolated from marine organisms combined with two common antibiotics, oxacillin and tetracycline, on three virulent bacterial strains. Initially, none of the tested lectins exhibited antibacterial effects when used individually. However, when combined with antibiotics, the lectins exhibited synergistic, additive, antagonistic, or no interaction. Overall, the tested lectins alone had no effect on the efficacy of oxacillin. On the other hand, different lectins in combination with tetracycline potentiated its antimicrobial effect. Lectins from red algae of the Bryothamnium genus, for example, exhibited the most significant synergistic effects, reducing the minimum inhibitory concentration (MIC) of tetracycline by up to 16 times. Lectins from the Hypnea genus also reduced the MIC of tetracycline. Our findings suggest that some lectins binding to complex carbohydrates containing fucosylated cores (α1-6) are excellent candidates to boost the efficacy of some antibiotics.
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Affiliation(s)
- Rômulo F Carneiro
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - Pedro Arthur S Tabosa
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - José Gabriel S Cândido
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - Vinícius Paulino P Menezes
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - Pedro Abilio V Rocha Júnior
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - Alexandre L Andrade
- Universidade Federal do Ceará, Departamento de Patologia e Medicina Legal, Laboratório Integrado de Biomoléculas - LIBS, Monsenhor Furtado, s/n, 60430-160 Fortaleza, CE, Brazil
| | - Mayron A Vasconcelos
- Universidade Federal do Ceará, Departamento de Patologia e Medicina Legal, Laboratório Integrado de Biomoléculas - LIBS, Monsenhor Furtado, s/n, 60430-160 Fortaleza, CE, Brazil
- Universidade Estadual do Ceará, Faculdade de Educação de Itapipoca (Facedi), Av. da Universidade, s/n, 62500-000 Itapipoca, CE, Brazil
| | - Edson H Teixeira
- Universidade Estadual do Ceará, Faculdade de Educação de Itapipoca (Facedi), Av. da Universidade, s/n, 62500-000 Itapipoca, CE, Brazil
| | - Celso S Nagano
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
| | - Alexandre H Sampaio
- Universidade Federal do Ceará, Departamento de Engenharia de Pesca, Laboratório de Biotecnologia Marinha - BioMar-Lab, Campus do Pici, s/n, Bloco 871, 60440-970 Fortaleza, CE, Brazil
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24
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Li Y, Liu X, Wang J, Li S. High-generation tetracyclines shifted microbial community composition and induced the emergence of antibiotic resistant bacteria in soil. JOURNAL OF HAZARDOUS MATERIALS 2024; 480:135757. [PMID: 39259998 DOI: 10.1016/j.jhazmat.2024.135757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 07/22/2024] [Accepted: 09/04/2024] [Indexed: 09/13/2024]
Abstract
Tetracyclines (TCs) have been widely detected in agricultural soil due to their widespread use in animal husbandry. The impact of low-generation TCs, i.e., the first- and second- generations, on soil ecosystem has attracted widespread attention. However, the dynamic response of soil microbial community to high-generation TCs, i.e., the third- and fourth- generations, remains largely unknown. Herein, we characterized the variations in the composition, diversity and succession of microbial community and the proliferation of antibiotic resistance genes (ARGs) under the stress of four generations of TCs in brown soil and red soil. The results demonstrated that the exposure of low- and high- generation TCs consistently decreased the alpha diversity and stimulated the succession rate of microbial community in soil. High-generation TCs strongly shifted microbial community composition by reducing community resilience. The complexity of microbial networks and cross-module associations were strengthened to cope with the stress of high-generation TCs in soil. The abundance of ARGs was exacerbated by 1.75 times in response to the fourth-generation TCs compared to control in brown soil. The potential bacterial hosts of ARGs were more diverse in brown soil exposed to high-generation TCs, but the dominant hosts were not changed. These results highlight the potential ecological risk of the newly developed antibiotics, which is helpful for a comprehensive risk assessment of emerging contaminants.
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Affiliation(s)
- Ying Li
- Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China
| | - Xiaoying Liu
- Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China
| | - Jie Wang
- Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China
| | - Si Li
- Beijing Key Laboratory of Farmland Soil Pollution Prevention and Remediation, College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China; Yantai Institute of China Agricultural University, Yantai 264670, China.
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25
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Mujtaba AG, Topuz B, Karakeçili A. Hybrid poly(lactide-co-glycolide) membranes incorporated with Doxycycline-loaded copper-based metal-organic nanosheets as antibacterial platforms. Biomed Mater 2024; 20:015011. [PMID: 39514973 DOI: 10.1088/1748-605x/ad906b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
The rise of antimicrobial resistance necessitates innovative strategies to combat persistent infections. Metal-organic frameworks (MOFs) have attracted significant attention as antibiotic carriers due to their high drug loading capacity and structural adaptability. In particular, 2D MOF nanosheets are emerging as a notable alternative to their traditional 3D relatives due to their remarkable advantages in enhanced surface area, flexibility and exposed active region properties. Herein, we synthesized 2D copper 1,4-benzendicarboxylate (CuBDC) nanosheets and utilized them as a carrier and controlled release system for Doxycycline (Doxy@CuBDC), for the first time. The Doxy@CuBDC nanosheets were subsequently incorporated into Poly(lactic-co-glycolic acid) (PLGA) electrospun membranes (Doxy@CuBDC/PLGA). The resultant bioactive fibrous membranes exhibited double-barrier controlled release properties, extending the Doxy release up to ∼9 d at pH 7.4 and 5.5. Significant inhibitory effects againstStaphylococcus aureusandEscherichia coliwere observed. The morphological analyses revealed the deformed bacterial cell structures on Doxy@CuBDC/PLGA membranes that indicates potent bactericidal activity. Furthermore, cytotoxicity assays demonstrated the non-toxic nature of the fabricated membranes, underscoring their potential use for biomedical applications. Overall, the hybrid antibacterial PLGA membranes present a promising strategy for combating microbial infections while maintaining biocompatibility and offer a versatile approach for biomedical material design and surface coatings (e.g. wound dressings, implants).
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Affiliation(s)
- Ayse Gunyakti Mujtaba
- Biotechnology Institute, Ankara University, Gümüşdere 60. Yıl Yerleşkesi Keçiören, Ankara 06135, Turkey
| | - Berna Topuz
- Department of Chemical Engineering, Faculty of Engineering, Ankara University, 06100 Tandoğan, Ankara, Turkey
| | - Ayşe Karakeçili
- Department of Chemical Engineering, Faculty of Engineering, Ankara University, 06100 Tandoğan, Ankara, Turkey
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26
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Wang Z, Li H. The tigecycline resistance mechanisms in Gram-negative bacilli. Front Cell Infect Microbiol 2024; 14:1471469. [PMID: 39635040 PMCID: PMC11615727 DOI: 10.3389/fcimb.2024.1471469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 10/14/2024] [Indexed: 12/07/2024] Open
Abstract
Tigecycline, hailed as a pivotal agent in combating multidrug-resistant bacterial infections, confronts obstacles posed by the emergence of resistance mechanisms in Gram-negative bacilli. This study explores the complex mechanisms of tigecycline resistance in Gram-negative bacilli, with a particular focus on the role of efflux pumps and drug modification in resistance. By summarizing these mechanisms, our objective is to provide a comprehensive understanding of tigecycline resistance in Gram-negative bacilli, thereby illuminating the evolving landscape of antimicrobial resistance. This review contributes to the elucidation of current existing tigecycline resistance mechanisms and provides insights into the development of effective strategies to manage the control of antimicrobial resistance in the clinical setting, as well as potential new targets for the treatment of tigecycline-resistant bacterial infections.
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Affiliation(s)
- Zhiren Wang
- Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, China
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Henan Li
- Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, China
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27
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Wang X, Teng G, Dong X, Dai Y, Wang W. The efficacy and safety of a simple 14-day vonoprazan-minocycline dual therapy for Helicobacter pylori eradication: a retrospective pilot study. Therap Adv Gastroenterol 2024; 17:17562848241299734. [PMID: 39569057 PMCID: PMC11577453 DOI: 10.1177/17562848241299734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 10/28/2024] [Indexed: 11/22/2024] Open
Abstract
Background Current eradication regimens are not ideal for Helicobacter pylori infected patients who have difficulty choosing antibiotics due to penicillin allergy or antibiotic resistance. Objective To explore the efficacy and safety of a simple vonoprazan-minocycline dual therapy (VM dual therapy) in H. pylori eradication. Design Clinical data of patients who were prescribed 14-day VM dual therapy were retrospectively collected. The included patients were 18-70 years old and positive for 13C urea breath test (13C-UBT). They were allergic to penicillin or had a history of repeated antibiotic exposure or had failed eradication with multiple regimens containing amoxicillin. VM dual therapy consists of vonoprazan 20 mg twice daily and minocycline 100 mg twice daily. 13C-UBT was repeated 4-6 weeks after treatment to evaluate the therapeutic outcome. Results Of the 88 enrolled patients, 54 were treatment naïve, 13 had one prior eradication failure, and 21 had multiple eradication failures. The overall intention to treat (ITT) and per-protocol (PP) eradication rates were 90.9% (95% CI: 82.4-95.7) and 95.2% (95% CI: 87.6-98.5). The ITT eradication rates were 90.7% (95% CI: 78.9-96.5) in treatment-naïve patients, 84.6% (95% CI: 53.7-97.3) in patients with one prior treatment failure, and 95.2% (95% CI: 74.1-99.8) in patients with multiple failures. The PP eradication rates were 94.2% (95% CI: 83.1-98.5), 91.7% (95% CI: 59.8-99.6), and 100%, respectively. The overall incidence of adverse events was 23.0%. The common adverse reactions were nausea and mild dizziness, which could be resolved without intervention. Conclusion Simple VM dual therapy exhibited a good eradication rate, low incidence of adverse effects, and good adherence. It is a potential new regimen for both first-line and rescue therapy.
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Affiliation(s)
- Xiaolei Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Guigen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xinhong Dong
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Weihong Wang
- Department of Gastroenterology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China
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28
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Caioni G, Reyes CP, Laurenti D, Chiaradia C, Dainese E, Mattioli R, Di Risola D, Santavicca E, Francioso A. Biochemistry and Future Perspectives of Antibiotic Resistance: An Eye on Active Natural Products. Antibiotics (Basel) 2024; 13:1071. [PMID: 39596764 PMCID: PMC11591525 DOI: 10.3390/antibiotics13111071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 10/31/2024] [Accepted: 11/05/2024] [Indexed: 11/29/2024] Open
Abstract
Antibiotic resistance poses a serious threat to the current healthcare system, negatively impacting the effectiveness of many antimicrobial treatments. The situation is exacerbated by the widespread overuse and abuse of available antibiotics, accelerating the evolution of resistance. Thus, there is an urgent need for novel approaches to therapy to overcome established resistance mechanisms. Plants produce molecules capable of inhibiting bacterial growth in various ways, offering promising paths for the development of alternative antibiotic medicine. This review emphasizes the necessity of research efforts on plant-derived chemicals in the hopes of finding and creating novel drugs that can successfully target resistant bacterial populations. Investigating these natural chemicals allows us to improve our knowledge of novel antimicrobial pathways and also expands our antibacterial repertoire with novel molecules. Simultaneously, it is still necessary to utilize present antibiotics sparingly; prudent prescribing practices must be encouraged to extend the effectiveness of current medications. The combination of innovative drug research and responsible drug usage offers an integrated strategy for managing the antibiotic resistance challenge.
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Affiliation(s)
- Giulia Caioni
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy; (G.C.); (E.D.)
| | - Carolina Pérez Reyes
- Department of Biochemistry, Microbiology, Cell Biology and Genetics, Instituto Universitario de Bio-Orgánica “Antonio González”, University of La Laguna, 38206 San Cristobal de La Laguna, Spain;
| | - Davide Laurenti
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Rome, Italy; (D.L.); (C.C.); (R.M.); (D.D.R.)
| | - Carmen Chiaradia
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Rome, Italy; (D.L.); (C.C.); (R.M.); (D.D.R.)
| | - Enrico Dainese
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy; (G.C.); (E.D.)
| | - Roberto Mattioli
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Rome, Italy; (D.L.); (C.C.); (R.M.); (D.D.R.)
| | - Daniel Di Risola
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Rome, Italy; (D.L.); (C.C.); (R.M.); (D.D.R.)
| | | | - Antonio Francioso
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy; (G.C.); (E.D.)
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29
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Ajose DJ, Adekanmbi AO, Kamaruzzaman NF, Ateba CN, Saeed SI. Combating antibiotic resistance in a one health context: a plethora of frontiers. ONE HEALTH OUTLOOK 2024; 6:19. [PMID: 39487542 PMCID: PMC11531134 DOI: 10.1186/s42522-024-00115-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 08/20/2024] [Indexed: 11/04/2024]
Abstract
One of the most significant medical advancements of the 20th century was the discovery of antibiotics, which continue to play a vital tool in the treatment and prevention of diseases in humans and animals. However, the imprudent use of antibiotics in all fields of One-Health and concerns about antibiotic resistance among bacterial pathogens have raised interest in antibiotic use restrictions on a global scale. Despite the failure of conventional antimicrobial agents, only about 15 new antibiotics have been introduced clinically since year 2000 to date. Moreover, there has been reports of resistance to some of these new antibiotics. This has necessitated a need to search for alternative strategies to combat antimicrobial resistant pathogens. Thus, this review compiles and evaluates the approaches-natural compounds, phage treatment, and nanomaterials-that are being used and/or suggested as the potential substitutes for conventional antibiotics.
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Affiliation(s)
- Daniel Jesuwenu Ajose
- Antimicrobial Resistance and Phage Biocontrol Research Group (AREPHABREG), Department of Microbiology, School of Biological Sciences, Faculty of Natural and Agricultural Sciences, North-West University, Private Mail Bag X2046, Mmabatho, 2735, South Africa.
- Food Security and Safety Focus Area, Faculty of Natural and Agricultural Sciences, North-West University, Private Bag X2046, Mmabatho, 2735, South Africa.
| | - Abimbola Olumide Adekanmbi
- Environmental Microbiology and Biotechnology Laboratory, Department of Microbiology, University of Ibadan, Ibadan, Nigeria
| | - Nor Fadhilah Kamaruzzaman
- Nanotechnology Research Group Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Kota Bharu, Kelantan, 16100, Malaysia
| | - Collins Njie Ateba
- Antimicrobial Resistance and Phage Biocontrol Research Group (AREPHABREG), Department of Microbiology, School of Biological Sciences, Faculty of Natural and Agricultural Sciences, North-West University, Private Mail Bag X2046, Mmabatho, 2735, South Africa
- Food Security and Safety Focus Area, Faculty of Natural and Agricultural Sciences, North-West University, Private Bag X2046, Mmabatho, 2735, South Africa
| | - Shamsaldeen Ibrahim Saeed
- College of Veterinary Medicine, University of Juba, P.O. Box 82, Juba, Central Equatoria, South Sudan.
- Department of microbiology, Faculty of Veterinary Science, University of Nyala, P.O. Box 155, Nyala, Sudan.
- Nanotechnology Research Group Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, Kota Bharu, Kelantan, 16100, Malaysia.
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Brdová D, Ruml T, Viktorová J. Mechanism of staphylococcal resistance to clinically relevant antibiotics. Drug Resist Updat 2024; 77:101147. [PMID: 39236354 DOI: 10.1016/j.drup.2024.101147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 08/17/2024] [Accepted: 08/26/2024] [Indexed: 09/07/2024]
Abstract
Staphylococcus aureus, a notorious pathogen with versatile virulence, poses a significant challenge to current antibiotic treatments due to its ability to develop resistance mechanisms against a variety of clinically relevant antibiotics. In this comprehensive review, we carefully dissect the resistance mechanisms employed by S. aureus against various antibiotics commonly used in clinical settings. The article navigates through intricate molecular pathways, elucidating the mechanisms by which S. aureus evades the therapeutic efficacy of antibiotics, such as β-lactams, vancomycin, daptomycin, linezolid, etc. Each antibiotic is scrutinised for its mechanism of action, impact on bacterial physiology, and the corresponding resistance strategies adopted by S. aureus. By synthesising the knowledge surrounding these resistance mechanisms, this review aims to serve as a comprehensive resource that provides a foundation for the development of innovative therapeutic strategies and alternative treatments for S. aureus infections. Understanding the evolving landscape of antibiotic resistance is imperative for devising effective countermeasures in the battle against this formidable pathogen.
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Affiliation(s)
- Daniela Brdová
- Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technicka 3, Prague 16628, Czech Republic.
| | - Tomáš Ruml
- Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technicka 3, Prague 16628, Czech Republic.
| | - Jitka Viktorová
- Department of Biochemistry and Microbiology, University of Chemistry and Technology, Technicka 3, Prague 16628, Czech Republic.
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Frazão DR, Matos-Souza JM, dos Santos VRN, Nazario RMF, Chemelo VDS, Bittencourt LO, Balbinot GDS, Collares FM, Gomes-Leal W, Ferreira RO, Rösing CK, Movila A, Lima RR. Minocycline reduces alveolar bone loss and bone damage in Wistar rats with experimental periodontitis. PLoS One 2024; 19:e0309390. [PMID: 39365804 PMCID: PMC11451981 DOI: 10.1371/journal.pone.0309390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/10/2024] [Indexed: 10/06/2024] Open
Abstract
This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis.
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Affiliation(s)
- Deborah Ribeiro Frazão
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - José Mario Matos-Souza
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Vinicius Ruan Neves dos Santos
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Rayssa Maite Farias Nazario
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Victoria dos Santos Chemelo
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Leonardo Oliveira Bittencourt
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Gabriela de Souza Balbinot
- Dental Materials Laboratory, School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Fabrício Mezzomo Collares
- Dental Materials Laboratory, School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Walace Gomes-Leal
- Laboratory of Experimental Neuroprotection and Neuroregeneration, Institute of Collective Health, Federal University of Western Pará (UFOPA), Santarém, Para, Brazil
| | - Railson Oliveira Ferreira
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
| | - Cassiano Kuchenbecker Rösing
- Department of Periodontology, School of Dentistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil
| | - Alexandru Movila
- Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, Indiana, United States of America
- Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Rafael Rodrigues Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Para, Brazil
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Pillay A, Vilfort K, Debra A, Katz SS, Thurlow CM, Joseph SJ, Lundy S, Ji A, Jaeyoung H, Workowski KA, Barrow RY, Danavall D, Pettus K, Chi KH, Kersh EN, Cao W, Chen CY, OS Surveillance Working Group. Molecular investigation of Treponema pallidum strains associated with ocular syphilis in the United States, 2016-2020. Microbiol Spectr 2024; 12:e0058124. [PMID: 39162489 PMCID: PMC11448083 DOI: 10.1128/spectrum.00581-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 06/25/2024] [Indexed: 08/21/2024] Open
Abstract
Ocular syphilis is a serious complication of Treponema pallidum infection that can occur at any stage of syphilis and affect any eye structure. It remains unknown if certain T. pallidum strains are associated with ocular infections; therefore, we performed genotyping and whole genome sequencing (WGS) to characterize strains from patients with ocular syphilis. Seventy-five ocular or non-ocular specimens from 55 ocular syphilis patients in 14 states within the United States were collected between February 2016 and November 2020. Sufficient T. pallidum DNA was available from nine patients for genotyping and three for WGS. Genotyping was done using the augmented Centers for Disease Control and Prevention typing scheme, and WGS was performed on Illumina platforms. Multilocus sequence typing allelic profiles were predicted from whole genome sequence data. T. pallidum DNA was detected in various specimens from 17 (30.9%) of the 55 patients, and typing was done on samples from 9 patients. Four complete strain types (14d10/g, 14b9/g, 14d9/g, and 14e9/f) and five partial types were identified. WGS was successful on samples from three patients and all three strains belonged to the SS14 clade of T. pallidum. Our data reveal that multiple strain types are associated with ocular manifestations of syphilis. While genotyping and WGS were challenging due to low amounts of T. pallidum DNA in specimens, we successfully performed WGS on cerebrospinal fluid, vitreous fluid, and whole blood.IMPORTANCESyphilis is caused by the spirochete Treponema pallidum. Total syphilis rates have increased significantly over the past two decades in the United States, and the disease remains a public health concern. In addition, ocular syphilis cases has also been on the rise, coinciding with the overall increase in syphilis rates. We conducted a molecular investigation utilizing traditional genotyping and whole genome sequencing over a 5-year period to ascertain if specific T. pallidum strains are associated with ocular syphilis. Genotyping and phylogenetic analysis show that multiple T. pallidum strain types are associated with ocular syphilis in the United States.
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Affiliation(s)
- Allan Pillay
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Kendra Vilfort
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Alyssa Debra
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Samantha S. Katz
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Charles M. Thurlow
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Sandeep J. Joseph
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Stephanie Lundy
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Andrew Ji
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Hong Jaeyoung
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Kimberly A. Workowski
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Department of Medicine, Emory University, Atlanta, Georgia, USA
| | - Roxanne Y. Barrow
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Damien Danavall
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Kevin Pettus
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Kai-Hua Chi
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Ellen N. Kersh
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Weiping Cao
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Cheng Y. Chen
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - OS Surveillance Working Group
- Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Department of Medicine, Emory University, Atlanta, Georgia, USA
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Gopakumar ST, Ramachandra KSS, Gangadharan S, Nair AV, Sachidanandan S, Prasad V, Purakal LV, Chakkalakkal GJ, Patil PK. In vitro efficacy of aquaculture antimicrobials and genetic determinants of resistance in bacterial isolates from tropical aquaculture disease outbreaks. Lett Appl Microbiol 2024; 77:ovae088. [PMID: 39271450 DOI: 10.1093/lambio/ovae088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 09/10/2024] [Accepted: 09/12/2024] [Indexed: 09/15/2024]
Abstract
Understanding the efficacy of antimicrobials against pathogens from clinical samples is critical for their responsible use. The manuscript presents in vitro efficacy and antimicrobial resistance (AMR) genes in seven species of fish pathogens from the disease outbreaks of Indian aquaculture against oxytetracycline, florfenicol, oxolinic acid, and enrofloxacin. In vitro efficacy was evaluated by minimum inhibitory concentration and minimum bactericidal concentration. The gene-specific PCR screened AMR genes against quinolones (qnrA, qnrB, and qnrS) and tetracyclines (tetM, tetS, tetA, tetC, tetB, tetD, tetE, tetH, tetJ, tetG, and tetY). The results showed that Aeromonas veronii (45%) showed the maximum resistance phenotype, followed by Streptococcus agalactiae (40%), Photobacterium damselae (15%), Vibrio parahaemolyticus (10%), and Vibrio vulnificus (5%). There was no resistance among Vibrio harveyi and Vibrio alginolyticus against the tested antimicrobials. The positive association between tetA, tetB, tetC, tetM, or a combination of these genes to oxytetracycline resistance and qnrS to quinolone resistance indicated their potential in surveillance studies. The prevalence of resistance phenotypes (16.43%) and evaluated AMR genes (2.65%) against aquaculture antimicrobials was low. The resistance phenotype pattern abundance was 0.143. All the isolates showed susceptibility to florfenicol. The results help with the appropriate drug selection against each species in aquaculture practices.
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Affiliation(s)
- Sumithra T Gopakumar
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Krupesha Sharma S Ramachandra
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Suja Gangadharan
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Anusree V Nair
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Suryagayathri Sachidanandan
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Vishnu Prasad
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Lailaja V Purakal
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - George J Chakkalakkal
- Fish Health Section, Marine Biotechnology, Fish Nutrition & Health Division, ICAR-Central Marine Fisheries Research Institute, Ernakulam North P.O., Kochi 682018, Kerala, India
| | - Prasanna K Patil
- Aquatic Animal Health and Environment Division, ICAR-Central Institute of Brackishwater Aquaculture, Raja Annamalai Puram, Chennai 600028, Tamil Nadu, India
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Pei Z, Liu Y, Zhao F, Wang H, Zhao J, Chen W, Lu W. Antibiotic Susceptibility Testing and Establishment of Tentative Species-Specific Microbiological Cut-off Values for Bifidobacteria Isolated from Chinese Population. Probiotics Antimicrob Proteins 2024; 16:1657-1672. [PMID: 37515711 DOI: 10.1007/s12602-023-10128-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2023] [Indexed: 07/31/2023]
Abstract
Bifidobacteria are commonly used as probiotics in the food industry. The resistance of Bifidobacterium species to antibiotics is closely linked to food safety. However, we still lack a system for the safety evaluation of antibiotic resistance in bifidobacteria, and genus-level microbiological cut-off values remain in use for the determination of phenotypic resistance of Bifidobacterium strains to a given antibiotic. Here, we collected a total of 422 gut-derived bifidobacterial strains isolated from Chinese population and identified their phenotypic resistance profiles against ampicillin, amoxicillin, ciprofloxacin, chloramphenicol, clindamycin, erythromycin, rifampicin, tetracycline, trimethoprim, and vancomycin. Different Bifidobacterium species were found to have varying tolerances to the same antibiotic; therefore, we further established species-specific cut-off values for bifidobacterial species to ten antibiotics. Species-specific rather than genus-specific cut-off values for species belonging to the same taxon were considered more suitable to determine the phenotypic resistance of a Bifidobacterium strain. Moreover, a comprehensive scanning of antibiotic resistance genes in all Bifidobacterium strains tested revealed that the existence of the tetracycline resistance gene tet(W) and the erythromycin/clindamycin resistance gene ErmX is closely related to host phenotypes. Our findings provide guidance and reference values at both phenotype and genotype levels for the safe application of bifidobacteria in the food industry and the development of probiotic resistance evaluation standards.
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Affiliation(s)
- Zhangming Pei
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Yufei Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Fang Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Hongchao Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, People's Republic of China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China.
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China.
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, People's Republic of China.
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Opazo-Capurro A, Xanthopoulou K, Arazo del Pino R, González-Muñoz P, Matus-Köhler M, Amsteins-Romero L, Jerez-Olate C, Hormazábal JC, Vera R, Aguilera F, Fuller S, Higgins PG, González-Rocha G. Co-Occurrence of Two Plasmids Encoding Transferable blaNDM-1 and tet(Y) Genes in Carbapenem-Resistant Acinetobacter bereziniae. Genes (Basel) 2024; 15:1213. [PMID: 39336804 PMCID: PMC11431271 DOI: 10.3390/genes15091213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/11/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open
Abstract
Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the blaNDM-1 and tet(Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile during the COVID-19 pandemic. Methods: Antibiotic susceptibility testing was conducted on UCO-553 and UCO-554. Both isolates underwent whole-genome sequencing to ascertain their sequence type (ST), core genome multilocus sequence-typing (cgMLST) profile, antibiotic resistance genes, plasmids, and mobile genetic elements. Conjugation experiments were performed for both isolates. Results: Both isolates exhibited broad resistance, including resistance to carbapenems, third-generation cephalosporins, fluoroquinolones, tetracycline, cotrimoxazole, and aminoglycosides. Both isolates belong to sequence type STPAS1761, with a difference of 17 out of 2984 alleles. Each isolate carried a 47,274 bp plasmid with blaNDM-1 and aph(3')-VI genes and two highly similar plasmids: a 35,184 bp plasmid with tet(Y), sul2, aph(6)-Id, and aph(3″)-Ib genes, and a 6078 bp plasmid containing the ant(2″)-Ia gene. Quinolone-resistance mutations were identified in the gyrA and parC genes of both isolates. Importantly, blaNDM-1 was located within a Tn125 transposon, and tet(Y) was embedded in a Tn5393 transposon. Conjugation experiments successfully transferred blaNDM-1 and tet(Y) into the A. baumannii ATCC 19606 strain, indicating the potential for horizontal gene transfer. Conclusions: This study highlights the critical role of plasmids in disseminating resistance genes in A. bereziniae and underscores the need for the continued genomic surveillance of this emerging pathogen. The findings emphasize the importance of monitoring A. bereziniae for its potential to cause difficult-to-treat infections and its capacity to spread resistance determinants against clinically significant antibiotics.
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Affiliation(s)
- Andrés Opazo-Capurro
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
| | - Kyriaki Xanthopoulou
- Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany; (K.X.); (R.A.d.P.)
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, D-50937 Cologne, Germany
| | - Rocío Arazo del Pino
- Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany; (K.X.); (R.A.d.P.)
| | - Paulina González-Muñoz
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
- Departamento de Ciencias Biológicas y Químicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Concepción 4070386, Chile
| | - Maximiliano Matus-Köhler
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
| | - Luis Amsteins-Romero
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
| | - Christian Jerez-Olate
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
- Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Concepción 4070386, Chile
| | | | - Rodrigo Vera
- Hospital de Urgencia Asistencia Pública, Santiago 8320000, Chile;
| | - Felipe Aguilera
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4070386, Chile; (F.A.); (S.F.)
- Centro de Biotecnología, Universidad de Concepción, Concepción 4070386, Chile
| | - Sebastián Fuller
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4070386, Chile; (F.A.); (S.F.)
| | - Paul G. Higgins
- Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, D-50937 Cologne, Germany; (K.X.); (R.A.d.P.)
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, D-50937 Cologne, Germany
- Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, D-50937 Cologne, Germany
| | - Gerardo González-Rocha
- Laboratorio de Investigación en Agentes Antibacterianos (LIAA), Universidad de Concepción, Concepción 4070386, Chile; (A.O.-C.); (P.G.-M.); (M.M.-K.); (L.A.-R.); (C.J.-O.)
- Grupo de Estudio en Resistencia Antimicrobiana (GRAM), Universidad de Concepción, Concepción 4070386, Chile
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Justo-Tirado M, Pérez-Herráez I, Escorihuela J, Arenal R, Zaballos-García E, Pérez-Prieto J. Harnessing sustainable nanoclusters for sensitive optical detection of tetracyclines and the underlying mechanism. NANOSCALE ADVANCES 2024:d4na00637b. [PMID: 39345791 PMCID: PMC11425532 DOI: 10.1039/d4na00637b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 09/06/2024] [Indexed: 10/01/2024]
Abstract
Simple and rapid sensing methods for the detection of antibiotics in drinks and foods are highly desirable due to the presence of these drugs in food products, as a consequence of extensive abuse of antibiotics in livestock production. In this study, we report a facile synthesis strategy of gold nanoclusters (AuNCs) passivated with N-acetyl-l-cysteine (AuNC@NAC). This nanocluster exhibits a fluorescence emission peak at 700 nm, which gradually decreases at increasing concentrations of antibiotics, such as tetracyclines. The limit of detection (LOD) was determined to be 0.8 ppm with a linear range of 0.1-140 μM (0.04-62 ppm). This method showcased exceptional selectivity in the detection of tetracyclines compared to anions, metallic cations and amino acids. The underlying mechanism has been elucidated, and the fluorescence quenching was found to be a combination of dynamic and static quenching mechanisms, with photoinduced electron transfer (PET) identified as the primary process for dynamic quenching.
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Affiliation(s)
- Miguel Justo-Tirado
- Instituto de Ciencia Molecular (ICMol), Universitat de València Catedrático José Beltrán 2 Paterna Valencia Spain
| | - Irene Pérez-Herráez
- Instituto de Ciencia Molecular (ICMol), Universitat de València Catedrático José Beltrán 2 Paterna Valencia Spain
| | - Jorge Escorihuela
- Departamento de Química Orgánica, University de València Av. Vicent Andres Estelles s/n Burjassot Spain
| | - Raúl Arenal
- Instituto de Nanociencia y Materiales de Aragon (INMA), CSIC-Universidad de Zaragoza 50009 Zaragoza Spain
- Laboratorio de Microscopias Avanzadas (LMA), U. Zaragoza C/Mariano Esquillor s/n 50018 Zaragoza Spain
- ARAID Foundation 50018 Zaragoza Spain
| | - Elena Zaballos-García
- Departamento de Química Orgánica, University de València Av. Vicent Andres Estelles s/n Burjassot Spain
| | - Julia Pérez-Prieto
- Instituto de Ciencia Molecular (ICMol), Universitat de València Catedrático José Beltrán 2 Paterna Valencia Spain
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Thorve M, Kishore N. Binding and displacement study of gentamicin, 5-fluorouracil, oxytetracycline and rolitetracycline with (BSA: Drug2) complex using spectroscopic and calorimetric techniques: Biophysical approach. Int J Biol Macromol 2024; 276:133677. [PMID: 38986981 DOI: 10.1016/j.ijbiomac.2024.133677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 04/02/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024]
Abstract
Understanding of energetics of interactions between drug and protein is essential in pharmacokinetics and pharmacodynamics study. The binding affinity (K) helps in investigating how tightly or loosely drug is bound to protein. The binding, displacement, conformational change and stability study of drugs- gentamicin (GM), 5-fluorouracil (5FU), oxytetracycline (OTC) and rolitetracycline (RTC) with bovine serum albumin (BSA) has been carried out in presence of each other drug by fluorescence, UV-visible spectroscopy, molecular docking, circular dichroism techniques and thermal denaturation method. The site marker study and docking methods have confirmed that 5FU and GM are able to bind at site 1 and OTC and RTC at site II of BSA. The order of their binding affinities with BSA for the binary system were as GM <5FU < OTC < RTC with the order of 102 < 103 < 105 < 105-6 M-1. The displacement study has shown that higher affinity drug decreases the equilibrium constant of another drug already in bound state with BSA if both these drugs are having the same binding site. Therefore 5FU, GM (binding site 1) drugs were not able to displace OTC and RTC (binding site 2) and vice-versa as they are binding at two different sites. The binding constant values were found to be decreasing with increasing temperature for all the systems involved which suggests static or mixed type of quenching, however can only confirmed with the help of TCSPC technique. The ΔG0 (binding energy) obtained from docking method were in accordance with the ITC method. From molecular docking we have determined the amino acid residues involved in binding process for binary and ternary systems by considering first rank minimum binding energy confirmation. From CD it has been observed that RTC causes most conformational change in secondary and tertiary structure of BSA due to the presence of pyrrole ring. OTC-RTC with higher affinity showed highest melting temperature Tm values while low affinity drugs in (5FU-GM) combination showed lowest Tm value. 5FU showed large endothermic denaturation enthalpy ΔHd0 due to the presence of highly electronegative fluorine atom in the pyridine analogue.
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Affiliation(s)
- Madhuri Thorve
- Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
| | - Nand Kishore
- Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
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Moulick S, Roy DN. Bioflavonoid Baicalein Modulates Tetracycline Resistance by Inhibiting Efflux Pump in Staphylococcus aureus. Microb Drug Resist 2024; 30:363-371. [PMID: 39133125 DOI: 10.1089/mdr.2024.0099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024] Open
Abstract
The rise in antibiotic resistance among bacterial pathogens, particularly Staphylococcus aureus, has become a critical global health issue, necessitating the search for novel antimicrobial agents. S. aureus uses various mechanisms to resist antibiotics, including the activation of efflux pumps, biofilm formation, and enzymatic modification of drugs. This study explores the potential of baicalein, a bioflavonoid from Scutellaria baicalensis, in modulating tetracycline resistance in S. aureus by inhibiting efflux pumps. The synergistic action of baicalein and tetracycline was evaluated through various assays. The minimum inhibitory concentration (MIC) of baicalein and tetracycline against S. aureus was 256 and 1.0 μg/mL, respectively. Baicalein at 64 μg/mL reduced the MIC of tetracycline by eightfold, indicating a synergistic effect (fractional inhibitory concentration index: 0.375). Time-kill kinetics demonstrated a 1.0 log CFU/mL reduction in bacterial count after 24 hours with the combination treatment. The ethidium bromide accumulation assay showed that baicalein mediated significant inhibition of efflux pumps, with a dose-dependent increase in fluorescence. In addition, baicalein inhibited DNA synthesis by 73% alone and 92% in combination with tetracycline. It also markedly reduced biofilm formation and the invasiveness of S. aureus into HeLa cells by 52% at 64 μg/mL. These findings suggest that baicalein enhances tetracycline efficacy and could be a promising adjunct therapy to combat multidrug-resistant S. aureus infections.
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Affiliation(s)
- Soumitra Moulick
- TCG Lifesciences Private Limited, Kolkata, India
- Department of Biotechnology, National Institute of Technology Raipur, Chhattisgarh, India
| | - Dijendra Nath Roy
- Department of Biotechnology, National Institute of Technology Raipur, Chhattisgarh, India
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Zhang X, Xiong S, Sathiyaseelan A, Zhang L, Lu Y, Chen Y, Jin T, Wang MH. Recent advances in photocatalytic nanomaterials for environmental remediation: Strategies, mechanisms, and future directions. CHEMOSPHERE 2024; 364:143142. [PMID: 39168377 DOI: 10.1016/j.chemosphere.2024.143142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/13/2024] [Accepted: 08/19/2024] [Indexed: 08/23/2024]
Abstract
Innovative and efficient strategies are urgently needed for wastewater treatment and environmental remediation. The photocatalytic degradation properties of photo-responsive nanomaterials (NMs) have become a prime candidate due to their low negative impact and photo-adjustability. Photocatalytic NMs vary in their degradation of different pollutants depending on the type of synthetic material, excitation light source, and physicochemical properties. Essentially, photocatalytic NMs excited by light produce reactive oxygen species (ROS) or metal ions that can degrade complex structure pollutants. Therefore, this review summarises the recent advances of photocatalytic NMs in the environmental application within the last 3 years, focusing on the development schemes, structural analyses, photocatalytic mechanisms, and the degradation effects of dyes, antibiotics, pesticides, phenolic compounds, metals, hormones, and other contaminants. The limitations and future directions are also explained. This review hopes to provide a possible pathway for the subsequent development of novel and efficient photocatalytic NMs to cope with complex and variable polluted environments.
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Affiliation(s)
- Xin Zhang
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
| | - Sirui Xiong
- College of Food Science and Engineering, Yanbian University, Yanji, Jilin, 133002, China.
| | - Anbazhagan Sathiyaseelan
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
| | - Lina Zhang
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
| | - Yuting Lu
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
| | - Yuting Chen
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
| | - Tieyan Jin
- College of Food Science and Engineering, Yanbian University, Yanji, Jilin, 133002, China.
| | - Myeong-Hyeon Wang
- Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
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Iconaru SL, Predoi D, Ciobanu CS, Negrila CC, Trusca R, Raaen S, Rokosz K, Ghegoiu L, Badea ML, Cimpeanu C. Novel Antimicrobial Agents Based on Zinc-Doped Hydroxyapatite Loaded with Tetracycline. Antibiotics (Basel) 2024; 13:803. [PMID: 39334978 PMCID: PMC11428947 DOI: 10.3390/antibiotics13090803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/20/2024] [Accepted: 08/23/2024] [Indexed: 09/30/2024] Open
Abstract
In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used for the sample's complex evaluation. Moreover, the biocompatibility of zinc-doped hydroxyapatite (ZnHAp) and ZnHApTe nanoparticles was evaluated with the aid of human fetal osteoblastic cells (hFOB 1.19 cell line). The results of the biological assays suggested that these nanoparticles hold great promise as potential candidates for the future development of novel biocompatible and antimicrobial agents for biomedical applications. The antimicrobial properties of the ZnHAp and ZnHApTe nanoparticles were assessed using the standard reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. The results of the in vitro antimicrobial assay demonstrated that both tested materials exhibited good antimicrobial activity. Additionally, these data also indicated that the antimicrobial effects of the ZnHAp nanoparticles were intensified by the presence of tetracycline (Te). Furthermore, the results also suggested that the antimicrobial activity of the samples increased with the incubation time.
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Affiliation(s)
- Simona Liliana Iconaru
- National Institute of Materials Physics, Atomistilor Street, No. 405A, 077125 Magurele, Romania
| | - Daniela Predoi
- National Institute of Materials Physics, Atomistilor Street, No. 405A, 077125 Magurele, Romania
| | - Carmen Steluta Ciobanu
- National Institute of Materials Physics, Atomistilor Street, No. 405A, 077125 Magurele, Romania
| | | | - Roxana Trusca
- National Centre for Micro and Nanomaterials, University Politehnica of Bucharest, 060042 Bucharest, Romania
| | - Steinar Raaen
- Department of Physics, Norwegian University of Science and Technology (NTNU), Realfagbygget E3-124 Høgskoleringen 5, NO 7491 Trondheim, Norway
| | - Krzysztof Rokosz
- Faculty of Electronics and Computer Science, Koszalin University of Technology, Śniadeckich 2, PL 75-453 Koszalin, Poland
| | - Liliana Ghegoiu
- National Institute of Materials Physics, Atomistilor Street, No. 405A, 077125 Magurele, Romania
| | - Monica Luminita Badea
- Faculty of Horticulture, University of Agronomic Sciences and Veterinary Medicine, 59 Marasti Boulevard, 011464 Bucharest, Romania
| | - Carmen Cimpeanu
- Faculty of Land Reclamation and Environmental Engineering, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 59 Marasti Boulevard, 011464 Bucharest, Romania
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Erb IK, Suarez C, Frank EM, Bengtsson-Palme J, Lindberg E, Paul CJ. Escherichia coli in urban marine sediments: interpreting virulence, biofilm formation, halotolerance, and antibiotic resistance to infer contamination or naturalization. FEMS MICROBES 2024; 5:xtae024. [PMID: 39246828 PMCID: PMC11378635 DOI: 10.1093/femsmc/xtae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 06/28/2024] [Accepted: 08/13/2024] [Indexed: 09/10/2024] Open
Abstract
Marine sediments have been suggested as a reservoir for pathogenic bacteria, including Escherichia coli. The origins, and properties promoting survival of E. coli in marine sediments (including osmotolerance, biofilm formation capacity, and antibiotic resistance), have not been well-characterized. Phenotypes and genotypes of 37 E. coli isolates from coastal marine sediments were characterized. The isolates were diverse: 30 sequence types were identified that have been previously documented in humans, livestock, and other animals. Virulence genes were found in all isolates, with more virulence genes found in isolates sampled from sediment closer to the effluent discharge point of a wastewater treatment plant. Antibiotic resistance was demonstrated phenotypically for one isolate, which also carried tetracycline resistance genes on a plasmid. Biofilm formation capacity varied for the different isolates, with most biofilm formed by phylogroup B1 isolates. All isolates were halotolerant, growing at 3.5% NaCl. This suggests that the properties of some isolates may facilitate survival in marine environments and can explain in part how marine sediments can be a reservoir for pathogenic E. coli. As disturbance of sediment could resuspend bacteria, this should be considered as a potential contributor to compromised bathing water quality at nearby beaches.
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Affiliation(s)
- Isabel K Erb
- Applied Microbiology, Department of Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden
- Sweden Water Research AB, Ideon Science Park, Scheelevägen 15, SE-223 70 Lund, Sweden
| | - Carolina Suarez
- Water Resources Engineering, Department of Building and Environmental Technology, Lund University, PO Box 118, SE-221 00 Lund, Sweden
| | - Ellinor M Frank
- Sweden Water Research AB, Ideon Science Park, Scheelevägen 15, SE-223 70 Lund, Sweden
- Water Resources Engineering, Department of Building and Environmental Technology, Lund University, PO Box 118, SE-221 00 Lund, Sweden
| | - Johan Bengtsson-Palme
- Division for Systems and Synthetic Biology, Department of Life Sciences, SciLifeLab, Chalmers University of Technology, Kemivägen 10, SE-412 96 Gothenburg, Sweden
- Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10, SE-413 46 Gothenburg, Sweden
- Centre for Antibiotic Resistance research (CARe), SE-413 45 Gothenburg, Sweden
| | - Elisabet Lindberg
- City of Helsingborg, Department of City Planning, Järnvägsgatan 22, SE-252 25 Helsingborg, Sweden
| | - Catherine J Paul
- Applied Microbiology, Department of Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden
- Water Resources Engineering, Department of Building and Environmental Technology, Lund University, PO Box 118, SE-221 00 Lund, Sweden
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Kaszecki E, Palberg D, Grant M, Griffin S, Dhanjal C, Capperauld M, Emery RJN, Saville BJ. Euglena mutabilis exists in a FAB consortium with microbes that enhance cadmium tolerance. Int Microbiol 2024; 27:1249-1268. [PMID: 38167969 PMCID: PMC11300505 DOI: 10.1007/s10123-023-00474-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/29/2023] [Accepted: 12/15/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Synthetic algal-fungal and algal-bacterial cultures have been investigated as a means to enhance the technological applications of the algae. This inclusion of other microbes has enhanced growth and improved stress tolerance of the algal culture. The goal of the current study was to investigate natural microbial consortia to gain an understanding of the occurrence and benefits of these associations in nature. The photosynthetic protist Euglena mutabilis is often found in association with other microbes in acidic environments with high heavy metal (HM) concentrations. This may suggest that microbial interactions are essential for the protist's ability to tolerate these extreme environments. Our study assessed the Cd tolerance of a natural fungal-algal-bacterial (FAB) association whereby the algae is E. mutabilis. RESULTS This study provides the first assessment of antibiotic and antimycotic agents on an E. mutabilis culture. The results indicate that antibiotic and antimycotic applications significantly decreased the viability of E. mutabilis cells when they were also exposed to Cd. Similar antibiotic treatments of E. gracilis cultures had variable or non-significant impacts on Cd tolerance. E. gracilis also recovered better after pre-treatment with antibiotics and Cd than did E. mutabilis. The recoveries were assessed by heterotrophic growth without antibiotics or Cd. In contrast, both Euglena species displayed increased chlorophyll production upon Cd exposure. PacBio full-length amplicon sequencing and targeted Sanger sequencing identified the microbial species present in the E. mutabilis culture to be the fungus Talaromyces sp. and the bacterium Acidiphilium acidophilum. CONCLUSION This study uncovers a possible fungal, algal, and bacterial relationship, what we refer to as a FAB consortium. The members of this consortium interact to enhance the response to Cd exposure. This results in a E. mutabilis culture that has a higher tolerance to Cd than the axenic E. gracilis. The description of this interaction provides a basis for explore the benefits of natural interactions. This will provide knowledge and direction for use when creating or maintaining FAB interactions for biotechnological purposes, including bioremediation.
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Affiliation(s)
- Emma Kaszecki
- Environmental and Life Science Graduate Program, Trent University, Peterborough, ON, Canada
| | - Daniel Palberg
- Environmental and Life Science Graduate Program, Trent University, Peterborough, ON, Canada
| | - Mikaella Grant
- Environmental and Life Science Graduate Program, Trent University, Peterborough, ON, Canada
| | - Sarah Griffin
- Forensic Science Department, Trent University, Peterborough, ON, Canada
| | - Chetan Dhanjal
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA
| | | | - R J Neil Emery
- Environmental and Life Science Graduate Program, Trent University, Peterborough, ON, Canada
- Department of Biology, Trent University, Peterborough, ON, Canada
| | - Barry J Saville
- Environmental and Life Science Graduate Program, Trent University, Peterborough, ON, Canada.
- Forensic Science Department, Trent University, Peterborough, ON, Canada.
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Zhu L, Xu Y, Li J, Lin G, Han X, Yi J, Jayaprada T, Zhou Z, Ying Y, Wang M. Environmentally persistent microbial contamination in agricultural soils: High risk of pathogenicity and antibiotic resistance. ENVIRONMENT INTERNATIONAL 2024; 190:108902. [PMID: 39059024 DOI: 10.1016/j.envint.2024.108902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/20/2024] [Accepted: 07/20/2024] [Indexed: 07/28/2024]
Abstract
Persistent microbial contamination commonly occurs in the environment. However, the characteristics and associated risks remain largely unknown. The coexistence of virulence factor genes (VFGs) and "last-resort" antibiotic resistance genes (LARGs) on human bacterial pathogens (HBPs) are notorious, creating ecological concerns and health risks. Herein, we explored the pathogenicity and antibiotic resistance levels of LARG-harboring HBPs in agricultural soils. Our findings revealed a high distribution level of VFGs and LARGs in soils (an absolute abundance up to 4.7 × 107 gene copies/g soil) by quantitative PCR (qPCR). Furthermore, most isolated LARG-harboring HBPs exhibited a 100 % lethality rate to Galleria mellonella. LARG-carrying plasmids had a low fitness cost to their host bacteria, implying the high adaptation of these plasmids within the HBPs. Most importantly, multiple LARG and VFG plasmid fusion and core genetic arrangements suggested that these LARG/VFG-linked plasmids endowed the stable and persistent horizontal spread of these genes in and/or cross the species and environments. This study not only unveiled high risk, multisource, compliance and stability aspects of environmentally persistent microbial contamination but also illuminated the importance of linking the phenotype-genotype-niche colonization of environmental microbial contamination within "One Health" framework.
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Affiliation(s)
- Lin Zhu
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Yongchang Xu
- Zhejiang Key Laboratory of Medical Epigenetics, Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China
| | - Jingpeng Li
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Guoping Lin
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Xuezhu Han
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Jiaming Yi
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Thilini Jayaprada
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Zhenchao Zhou
- College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yiqian Ying
- Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
| | - Meizhen Wang
- International Science and Technology Cooperation Platform for Low-Carbon Recycling of Waste and Green Development & Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling, School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310012, China.
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Dhiman S, Ramirez D, Arora R, Arthur G, Schweizer F. Enhancing outer membrane permeability of tetracycline antibiotics in P. aeruginosa using TOB-CIP conjugates. RSC Med Chem 2024:d4md00329b. [PMID: 39131887 PMCID: PMC11305099 DOI: 10.1039/d4md00329b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/20/2024] [Indexed: 08/13/2024] Open
Abstract
Pseudomonas aeruginosa is an opportunistic critical 'priority 1' Gram-negative bacterium that poses a severe threat to public healthcare due to rising antibiotic resistance. Particularly, low membrane permeability and overexpression of efflux pumps in P. aeruginosa lead to intrinsic resistance that compromises the antibacterial activity of antibiotics. The broad-spectrum antibiotics class, tetracyclines, are rarely used to treat P. aeruginosa infections. In the present study, we describe a series of tobramycin-ciprofloxacin (TOB-CIP) conjugates in which the carboxylic acid of ciprofloxacin is linked to the aminoglycoside tobramycin using various tethers thereby generating a cationic amphiphile. The emerging amphiphilic conjugates potentiate tetracycline antibiotics including minocycline, doxycycline, tigecycline, and eravacycline against multidrug-resistant P. aeruginosa isolates. The structure-activity relationship investigation indicates that the flexible hydrophobic C12 carbon-chain linker in TOB-CIP conjugate 1a is an optimal potentiator of tetracyclines against tetracycline-resistant and -susceptible strains of P. aeruginosa. Furthermore, conjugate 1a consistently synergized with the 3rd generation tetracycline, eravacycline, in P. aeruginosa PAO1 in the presence of up to 25% fetal bovine serum (FBS).
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Affiliation(s)
- Shiv Dhiman
- Department of Chemistry, Faculty of Science, University of Manitoba Winnipeg Manitoba R3T 2N2 Canada
| | - Danyel Ramirez
- Department of Chemistry, Faculty of Science, University of Manitoba Winnipeg Manitoba R3T 2N2 Canada
| | - Rajat Arora
- Department of Chemistry, Faculty of Science, University of Manitoba Winnipeg Manitoba R3T 2N2 Canada
| | - Gilbert Arthur
- Department of Biochemistry and Medical Genetics, University of Manitoba Winnipeg Manitoba R3E 0J9 Canada
| | - Frank Schweizer
- Department of Chemistry, Faculty of Science, University of Manitoba Winnipeg Manitoba R3T 2N2 Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba Winnipeg Manitoba R3E 0J9 Canada
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Li X, Wang M, Denk T, Buschauer R, Li Y, Beckmann R, Cheng J. Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. Nat Commun 2024; 15:5481. [PMID: 38942792 PMCID: PMC11213857 DOI: 10.1038/s41467-024-49797-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 06/18/2024] [Indexed: 06/30/2024] Open
Abstract
Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy.
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Affiliation(s)
- Xiang Li
- Minhang Hospital & Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China
| | - Mengjiao Wang
- Minhang Hospital & Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China
| | - Timo Denk
- Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Robert Buschauer
- Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Yi Li
- Minhang Hospital & Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China
| | - Roland Beckmann
- Gene Center, Ludwig-Maximilians-Universität München, Munich, Germany.
| | - Jingdong Cheng
- Minhang Hospital & Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai, China.
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Klenotic PA, Yu EW. Structural analysis of resistance-nodulation cell division transporters. Microbiol Mol Biol Rev 2024; 88:e0019823. [PMID: 38551344 PMCID: PMC11332337 DOI: 10.1128/mmbr.00198-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2024] Open
Abstract
SUMMARYInfectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.
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Affiliation(s)
- Philip A. Klenotic
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - Edward W. Yu
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
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Tantalo LC, Luetkemeyer A, P Lieberman NA, Nunley BE, Avendaño C, Greninger AL, Celum C, Giacani L. Long-term in vitro exposure of Treponema pallidum to sub-bactericidal doxycycline did not induce resistance: Implications for doxy-PEP and syphilis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.27.600921. [PMID: 38979216 PMCID: PMC11230427 DOI: 10.1101/2024.06.27.600921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Doxycycline post-exposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistant Treponema pallidum ( T. pallidum ) strains. To assess whether resistance to doxycycline could be induced in this pathogen, we exposed the SS14 strain in vitro both intermittently and continuously to a sub-bactericidal doxycycline concentration that still exerts antibiotic pressure. During and after each exposure experiment, we assessed the doxycycline minimal inhibitory concentration in test and control treponemes and performed whole genome sequencing, concluding that no resistance developed. This work suggests that doxycycline-resistant T. pallidum is not an immediate threat for doxy-PEP implementation.
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Hu M, Yang W, Yan R, Chi J, Xia Q, Yang Y, Wang Y, Sun L, Li P. Co-evolution of vaginal microbiome and cervical cancer. J Transl Med 2024; 22:559. [PMID: 38863033 PMCID: PMC11167889 DOI: 10.1186/s12967-024-05265-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/29/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Exploration of adaptive evolutionary changes at the genetic level in vaginal microbial communities during different stages of cervical cancer remains limited. This study aimed to elucidate the mutational profile of the vaginal microbiota throughout the progression of cervical disease and subsequently establish diagnostic models. METHODS This study utilized a metagenomic dataset consisting of 151 subjects classified into four categories: invasive cervical cancer (CC) (n = 42), cervical intraepithelial neoplasia (CIN) (n = 43), HPV-infected (HPVi) patients without cervical lesions (n = 34), and healthy controls (n = 32). The analysis focused on changes in microbiome abundance and extracted information on genetic variation. Consequently, comprehensive multimodal microbial signatures associated with CC, encompassing taxonomic alterations, mutation signatures, and enriched metabolic functional pathways, were identified. Diagnostic models for predicting CC were established considering gene characteristics based on single nucleotide variants (SNVs). RESULTS In this study, we screened and analyzed the abundances of 18 key microbial strains during CC progression. Additionally, 71,6358 non-redundant mutations were identified, predominantly consisting of SNVs that were further annotated into 25,773 genes. Altered abundances of SNVs and mutation types were observed across the four groups. Specifically, there were 9847 SNVs in the HPV-infected group and 14,892 in the CC group. Furthermore, two distinct mutation signatures corresponding to the benign and malignant groups were identified. The enriched metabolic pathways showed limited similarity with only two overlapping pathways among the four groups. HPVi patients exhibited active nucleotide biosynthesis, whereas patients with CC demonstrated a significantly higher abundance of signaling and cellular-associated protein families. In contrast, healthy controls showed a distinct enrichment in sugar metabolism. Moreover, biomarkers based on microbial SNV abundance displayed stronger diagnostic capability (cc.AUC = 0.87) than the species-level biomarkers (cc.AUC = 0.78). Ultimately, the integration of multimodal biomarkers demonstrated optimal performance for accurately identifying different cervical statuses (cc.AUC = 0.86), with an acceptable performance (AUC = 0.79) in the external testing set. CONCLUSIONS The vaginal microbiome exhibits specific SNV evolution in conjunction with the progression of CC, and serves as a specific biomarker for distinguishing between different statuses of cervical disease.
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Affiliation(s)
- Menglu Hu
- School of Medicine, Southeast University, Nanjing, China
| | - Wentao Yang
- School of Medicine, Southeast University, Nanjing, China
| | - Ruiyi Yan
- Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, 100730, China
| | - Jiayu Chi
- School of Medicine, Southeast University, Nanjing, China
| | - Qi Xia
- School of Medicine, Southeast University, Nanjing, China
| | - Yilin Yang
- School of Medicine, Southeast University, Nanjing, China
| | - Yinhan Wang
- Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, 100730, China.
| | - Lejia Sun
- Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, 100730, China.
- The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
| | - Ping Li
- Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
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Neagu R, Popovici V, Ionescu LE, Ordeanu V, Biță A, Popescu DM, Ozon EA, Gîrd CE. Phytochemical Screening and Antibacterial Activity of Commercially Available Essential Oils Combinations with Conventional Antibiotics against Gram-Positive and Gram-Negative Bacteria. Antibiotics (Basel) 2024; 13:478. [PMID: 38927145 PMCID: PMC11200707 DOI: 10.3390/antibiotics13060478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/18/2024] [Accepted: 05/22/2024] [Indexed: 06/28/2024] Open
Abstract
The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs), Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO), against the most-known MDR Gram-positive and Gram-negative bacteria-Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853)-alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex compositions. Then, their antibacterial activity-expressed as the inhibition zone diameter (IZD) value (mm)-was investigated in vitro by the diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µL of sample and sterile borosilicate glass cylinders loaded with 100 µL; the minimum inhibitory concentration (MIC) value (µg/mL) for each EO was calculated from the IZD values (mm) measured after 24 h. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on the activity of three conventional antibacterial drugs-Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC)-was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO showed additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other two (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases involved antagonism between the constituents included in the double and triple combinations, and the EOs with the strongest antibacterial activities belonged to the highest antagonistic combinations. A consistent statistical analysis supported our results, showing that the EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.
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Affiliation(s)
- Răzvan Neagu
- Department of Pharmacognosy, Phytochemistry, and Phytotherapy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania; (R.N.); (C.E.G.)
- Regenerative Medicine Laboratory, “Cantacuzino” National Military Medical Institute for Research and Development, 103 Spl. Independentei, 050096 Bucharest, Romania;
| | - Violeta Popovici
- Center for Mountain Economics, “Costin C. Kiriţescu” National Institute of Economic Research (INCE-CEMONT), Romanian Academy, 725700 Vatra-Dornei, Romania
| | - Lucia-Elena Ionescu
- Experimental Microbiology Laboratory, “Cantacuzino” National Military Medical Institute for Research and Development, 103 Spl. Independentei, 050096 Bucharest, Romania
| | - Viorel Ordeanu
- Faculty of Pharmacy, “Titu Maiorescu” University, 16 Sincai, 040314 Bucharest, Romania;
| | - Andrei Biță
- Department of Pharmacognosy & Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Diana Mihaela Popescu
- Regenerative Medicine Laboratory, “Cantacuzino” National Military Medical Institute for Research and Development, 103 Spl. Independentei, 050096 Bucharest, Romania;
| | - Emma Adriana Ozon
- Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania;
| | - Cerasela Elena Gîrd
- Department of Pharmacognosy, Phytochemistry, and Phytotherapy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania; (R.N.); (C.E.G.)
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Zhou K, Li CL, Zhang H, Suo BJ, Zhang YX, Ren XL, Wang YX, Mi CM, Ma LL, Zhou LY, Tian XL, Song ZQ. Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis. World J Gastroenterol 2024; 30:2354-2368. [PMID: 38813048 PMCID: PMC11130572 DOI: 10.3748/wjg.v30.i17.2354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/04/2024] [Accepted: 04/10/2024] [Indexed: 04/30/2024] Open
Abstract
BACKGROUND Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.
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Affiliation(s)
- Kai Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Cai-Ling Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Hua Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Bao-Jun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yu-Xin Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xin-Lu Ren
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yu-Xin Wang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Chang-Min Mi
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Ling-Ling Ma
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Li-Ya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Xue-Li Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Zhi-Qiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
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