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Birara S, Kumar Yadav V, Kumar Jena A, Bhattacharyya S, Metre RK. Antimicrobial Potential of a Formazanate-Based Mercury(II) Complex: In Vitro- and In Silico-Based Insights. Chempluschem 2024:e202400696. [PMID: 39714804 DOI: 10.1002/cplu.202400696] [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: 11/05/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Herein, we present a distorted square pyramidal mercury complex, [HgII(L)Cl] (1), based on a quinoline-substituted formazan ligand LH[3-Cyano-1,5-(quinolin-8-yl)formazan], which was evaluated for its anti-bacterial activity in vitro. Complex 1 was prepared by refluxing 3-Cyano-1,5-(quinolin-8-yl)formazan ligand and mercury chloride(II) in equimolar quantity and was characterized utilizing a range of analytical methods, including single crystal X-ray diffraction (SCXRD) technique. The crystal packing in complex 1 has been elucidated using supramolecular investigations, which have shown the presence of fascinating Hg-Cl⋅⋅⋅Hg intermolecular spodium bonds of the order 3.348 Å. The antimicrobial activity of the formazanate-based mercury(II) complex (1) was assessed against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial pathogens. In addition, the plausible therapeutic target of the formazanate-based mercury(II) complex was determined through in silico pharmacophore-guided rational drug designing approach. Based on the in silico results, a conceivable molecular mechanism of the observed bactericidal action of the newly synthesized [HgII(L)Cl] complex (1) has also been suggested.
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Affiliation(s)
- Sunita Birara
- Department of Chemistry, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
| | - Vinay Kumar Yadav
- Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
| | - Abinash Kumar Jena
- Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
| | - Sudipta Bhattacharyya
- Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
| | - Ramesh K Metre
- Department of Chemistry, Indian Institute of Technology, Jodhpur, Rajasthan 342037, India
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Abdelmajed MA, El-Din KMB, Attia TZ, Omar MA. Full green assay of parenteral dosage forms of polymyxins utilizing xanthene dye: application to content uniformity testing. BMC Chem 2024; 18:158. [PMID: 39192355 DOI: 10.1186/s13065-024-01261-9] [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: 03/04/2024] [Accepted: 08/05/2024] [Indexed: 08/29/2024] Open
Abstract
Due to the lack of other treatment options, a rebirth of polymyxins is urgently required. Colistin (also called polymyxin E) and polymyxin B are the only two examples of this antibiotic class that were effectively employed in such critical situations. In the present work, both of the two studied medications were quantified via a simple, green, and non-extracting spectrophotometric approach based on the formation of ion-pair complexes with Erythrosine B. Without using any organic solvents, the pink color of the created complexes was detected at wavelength = 558 nm. To achieve the highest intensity of absorbance, optimum conditions were established by the screening of many experimental factors such as pH, buffer volume, the volume of Erythrosine B, and the time consumed to undergo the reaction. For Colistin and Polymyxin B respectively, Beer-Lambert's law was observed at the concentration ranges of 1-6, 1-9 µg mL- 1. The technique was approved and validated following ICH recommendations. Lastly, the suggested approach has been successfully implemented to quantify the cited medications colorimetrically, for the first time, in their parenteral dosage forms with excellent recoveries. Also, Content uniformity testing was implemented.
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Affiliation(s)
- Mahmoud A Abdelmajed
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Deraya University, New Minia, Egypt.
| | - Khalid M Badr El-Din
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Tamer Z Attia
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
| | - Mahmoud A Omar
- Department of Analytical Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Medinah, Saudi Arabia
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Jarab AS, Al-Alawneh TO, Alshogran OY, Heshmeh SA, Mukattash TL, Naser YA, Alefishat E. Knowledge and attitude of healthcare prescribers and pharmacists toward antimicrobial stewardship program and the barriers for its implementation. Antimicrob Resist Infect Control 2024; 13:35. [PMID: 38566242 PMCID: PMC10985862 DOI: 10.1186/s13756-024-01382-9] [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: 04/10/2023] [Accepted: 02/10/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Antimicrobial stewardship (ASP) is considered a key prevention strategy in addressing the worldwide concern of accelerating antimicrobial resistance. Limited research is available regarding healthcare providers' knowledge and attitude toward antimicrobial stewardship and the barriers for its implementation. METHODS The present cross-sectional study was conducted on pharmacists and healthcare prescribers (HCPs) in different hospital sites across Jordan. A validated survey was used to evaluate HCPs and pharmacists' knowledge, and attitudes towards ASP and the barriers for its implementation. Logistic and linear regression were conducted to identify the factors associated with knowledge and attitude toward ASP, respectively. RESULTS A total of 603 participants, 69 (11.4%) pharmacists and 534 (88.6%) HCPs completed the study questionnaire, with a response rate of 80.4%. The overall mean knowledge about ASP was 7.16 out of 10, ranging from 0 to 10 (SD 2.22). Being a pharmacist and increased awareness/familiarity about ASP were associated with improved ASP knowledge. The overall average attitude score was = 3.8 ± 0.49 (range: 1.8-4.8). Results revealed that being a pharmacist and improved knowledge were associated with improved attitude toward ASP. Lack of specialized staff with expertise in ASP and lack of access to education and training programs were the major barriers hinder ASP implementation. CONCLUSION Despite the reasonable knowledge and the positive attitude toward the ASP, several barriers were reported, particularly by the pharmacists. Therefore, promoting the presence of adequately skilled healthcare personnel, creating easily accessible online courses, and establishing a comprehensive database of ASP resources are all suggested approaches to improve the application of ASP in healthcare settings.
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Affiliation(s)
- Anan S Jarab
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, 22110, Irbid, P.O. Box 3030, Jordan
- College of Pharmacy, AL Ain University, Abu Dhabi, United Arab Emirates
| | - Tasneem O Al-Alawneh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, 22110, Irbid, P.O. Box 3030, Jordan
| | - Osama Y Alshogran
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, 22110, Irbid, P.O. Box 3030, Jordan
| | - Shrouq Abu Heshmeh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, 22110, Irbid, P.O. Box 3030, Jordan
| | - Tareq L Mukattash
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, 22110, Irbid, P.O. Box 3030, Jordan
| | - Yara A Naser
- School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Northern Ireland, 97 Lisburn Road, BT9 7BL, Belfast, UK
| | - Eman Alefishat
- Department of Medical Sciences, College of Medicine and Health Science, Khalifa University of Science and Technology, 127788, Abu Dhabi, United Arab Emirates.
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan, 11942, Amman, Jordan.
- Center for Biotechnology, Khalifa University of Science and Technology, 127788, Abu Dhabi, United Arab Emirates.
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4
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Hossain MJ, Azad AK, Shahid MSB, Shahjahan M, Ferdous J. Prevalence, antibiotic resistance pattern for bacteriuria from patients with urinary tract infections. Health Sci Rep 2024; 7:e2039. [PMID: 38617042 PMCID: PMC11009458 DOI: 10.1002/hsr2.2039] [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: 10/26/2023] [Revised: 03/09/2024] [Accepted: 03/26/2024] [Indexed: 04/16/2024] Open
Abstract
Background and Aims Antibiotic resistance presents a significant global public health challenge, particularly for urinary tract infections (UTIs), and is notably severe in developing countries. Surveillance of the antimicrobial susceptibility patterns of UTI-causing bacteria is crucial for effective treatment selection. This study aimed to analyze these patterns in bacteria isolated from the urine samples of patients at Mughda Medical College Hospital, Dhaka, Bangladesh. Methods A retrospective study (January 2019 to December 2020) at Mugdha Medical College and Hospital, Dhaka, examined clinical and laboratory data from patients with positive urine cultures (≥105 CFU/mL). The study classified patients into four age groups: children (1-<18 years), young adults (18-<33 years), middle-aged adults (33-50 years), and old adults (>50 years). The standard Kirby-Bauer method was used to assess antibiotic sensitivity to 28 common antibiotics. Results Among 243 positive urine cultures in both community- and hospital-acquired UTIs, Escherichia coli was the most common uropathogen (65.84%), followed by Klebsiella spp. (12.34%), Enterococcus spp. (8.23%), and other types of bacteria. Conclusion Old adults are particularly vulnerable to UTIs, with E. coli being the predominant causative agent in the study region. The observed antimicrobial resistance patterns underscore the necessity of judicious antibiotic selection to effectively treat UTIs across different age groups.
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Affiliation(s)
- Md. Jubayer Hossain
- Population Health Studies Division, Center for Health Innovation, ResearchAction, and Learning – Bangladesh (CHIRAL Bangladesh)DhakaBangladesh
| | - Abul Kalam Azad
- Department of MicrobiologyJagannath UniversityDhakaBangladesh
| | - Md. Shahadat Bin Shahid
- Population Health Studies Division, Center for Health Innovation, ResearchAction, and Learning – Bangladesh (CHIRAL Bangladesh)DhakaBangladesh
- Department of MicrobiologyJagannath UniversityDhakaBangladesh
| | - Muhibullah Shahjahan
- Population Health Studies Division, Center for Health Innovation, ResearchAction, and Learning – Bangladesh (CHIRAL Bangladesh)DhakaBangladesh
- Department of MicrobiologyJagannath UniversityDhakaBangladesh
| | - Jannatul Ferdous
- Department of Transfusion MedicineMugdha Medical College and HospitalDhakaBangladesh
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Yalkut K, Ben Ali Hassine S, Basaran E, Kula C, Ozcan A, Avci FG, Keskin O, Sariyar Akbulut B, Ozbek P. Attenuation of Type IV pili activity by natural products. J Biomol Struct Dyn 2024:1-11. [PMID: 38305801 DOI: 10.1080/07391102.2024.2310781] [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: 11/08/2023] [Accepted: 01/20/2024] [Indexed: 02/03/2024]
Abstract
The virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Kerem Yalkut
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Soumaya Ben Ali Hassine
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
- Department of Bioengineering, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul, Turkey
| | - Esra Basaran
- Graduate School of Sciences and Engineering, Koc University, Istanbul, Turkey
| | - Ceyda Kula
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Aslıhan Ozcan
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Fatma Gizem Avci
- Department of Bioengineering, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul, Turkey
| | - Ozlem Keskin
- Graduate School of Sciences and Engineering, Koc University, Istanbul, Turkey
| | - Berna Sariyar Akbulut
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Pemra Ozbek
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
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Azarian M, Junyusen T, Sutapun W. Biogenic Vaterite Calcium Carbonate-Silver/Poly(Vinyl Alcohol) Film for Wound Dressing. ACS OMEGA 2024; 9:955-969. [PMID: 38222591 PMCID: PMC10785620 DOI: 10.1021/acsomega.3c07135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/27/2023] [Accepted: 11/22/2023] [Indexed: 01/16/2024]
Abstract
Vaterite, a spherical polymorph of CaCO3, shows potential as a carrier for the stable and controlled release of silver nanoparticles (AgNPs), preventing their aggregation or loss of efficacy during application. Furthermore, the embedding of CaCO3-Ag in a poly(vinyl alcohol) (PVA) matrix helps effectively encapsulate and protect the CaCO3-Ag microspheres and provides mechanical stability for better contact with the wound surface. This article focuses on the fabrication of an antimicrobial and biocompatible absorbent film embedded with precipitated biogenic vaterite CaCO3-Ag microspheres. The impact of vaterite CaCO3-Ag on the physical, chemical, nanomechanical, biocompatibility, and antimicrobial properties of the PVA films was investigated. The morphology study revealed a bilayer film structure with an inactive and active surface containing homogeneously distributed vaterite CaCO3-Ag. The X-ray photoelectron spectroscopy (XPS) analysis of the spin-orbit splitting in the Ag 3d5/2 and Ag 3d3/2 peaks indicated the presence of both metallic and ionic states of silver in vaterite CaCO3-Ag prior to its incorporation into the PVA polymer matrix. However, upon embedding in the PVA matrix, a subsequent transformation to solely ionic states was observed. The nanomechanical properties of PVA improved, and the reduced modulus and hardness increased to 14.62 ± 5.23 and 0.64 ± 0.29 GPa, respectively. The films demonstrate a significant activity toward Gram-negative Escherichia coli bacteria. The release of AgNPs was studied in both open and closed systems at pH 6, mimicking the pH environment of the wound, and it demonstrated a dependency on the type of capping agent used for synthesis and loading of AgNPs. The results further revealed the biocompatibility of the prepared films with human dermal fibroblast cells at a concentration of ≤5 mg/mL, making them applicable and functional for wound dressing applications.
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Affiliation(s)
- Mohammad
Hossein Azarian
- Research
Center for Biocomposite Materials for Medical, Agricultural and Food
Industry, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Tiraporn Junyusen
- School
of Agricultural Engineering, Institute of Engineering, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Wimonlak Sutapun
- Research
Center for Biocomposite Materials for Medical, Agricultural and Food
Industry, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
- School
of Polymer Engineering, Suranaree University
of Technology, Nakhon Ratchasima 30000, Thailand
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Thesnor V, Molinié R, Giebelhaus RT, de la Mata Espinosa AP, Harynuk JJ, Bénimélis D, Vanhoye B, Dunyach-Rémy C, Sylvestre M, Cheremond Y, Meffre P, Cebrián-Torrejón G, Benfodda Z. Antibacterial Activity and Untargeted Metabolomics Profiling of Acalypha arvensis Poepp. Molecules 2023; 28:7882. [PMID: 38067611 PMCID: PMC10708339 DOI: 10.3390/molecules28237882] [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: 10/02/2023] [Revised: 11/19/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
The search for potent antimicrobial compounds is critical in the face of growing antibiotic resistance. This study explores Acalypha arvensis Poepp. (A. arvensis), a Caribbean plant traditionally used for disease treatment. The dried plant powder was subjected to successive extractions using different solvents: hexane (F1), dichloromethane (F2), methanol (F3), a 50:50 mixture of methanol and water (F4), and water (F5). Additionally, a parallel extraction was conducted using a 50:50 mixture of methanol and chloroform (F6). All the fractions were evaluated for their antimicrobial activity, and the F6 fraction was characterized using untargeted metabolomics using SPME-GC×GC-TOFMS. The extracts of A. arvensis F3, F4, and F5 showed antibacterial activity against Staphylococcus aureus ATCC 25923 (5 mg/mL), MRSA BA22038 (5 mg/mL), and Pseudomonas aeruginosa ATCC 27853 (10 mg/mL), and fraction F6 showed antibacterial activity against Staphylococcus aureus ATCC 29213 (2 mg/mL), Escherichia coli ATCC 25922 (20 mg/mL), Pseudomonas aeruginosa ATCC 27853 (10 mg/mL), Enterococcus faecalis ATCC 29212 (10 mg/mL), Staphylococcus aureus 024 (2 mg/mL), and Staphylococcus aureus 003 (2 mg/mL). Metabolomic analysis of F6 revealed 2861 peaks with 58 identified compounds through SPME and 3654 peaks with 29 identified compounds through derivatization. The compounds included methyl ester fatty acids, ethyl ester fatty acids, terpenes, ketones, sugars, amino acids, and fatty acids. This study represents the first exploration of A. arvensis metabolomics and its antimicrobial potential, providing valuable insights for plant classification, phytochemical research, and drug discovery.
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Affiliation(s)
- Valendy Thesnor
- UPR Chrome, University Nimes, CEDEX 1, 30021 Nîmes, France; (V.T.); (D.B.); (P.M.)
- COVACHIM-M2E Laboratory EA 3592, Department of Chemistry, UFR SEN, Fouillole Campus, University of Antilles, CEDEX, 97110 Pointe-à-Pitre, France;
- URE, Université d’État d’Haïti, Port-au-Prince HT6110, Haiti;
| | - Roland Molinié
- UMR INRAE 1158 Transfrontalière BioEcoAgro, BIOlogie des Plantes et Innovation (BIOPI), UPJV, UFR de Pharmacie, 80037 Amiens, France; (R.M.); (B.V.)
| | - Ryland T. Giebelhaus
- Department of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, Canada; (R.T.G.); (A.P.d.l.M.E.); (J.J.H.)
- The Metabolomics Innovation Centre, Edmonton, AB T6G 2N4, Canada
| | - A. Paulina de la Mata Espinosa
- Department of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, Canada; (R.T.G.); (A.P.d.l.M.E.); (J.J.H.)
- The Metabolomics Innovation Centre, Edmonton, AB T6G 2N4, Canada
| | - James J. Harynuk
- Department of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, Canada; (R.T.G.); (A.P.d.l.M.E.); (J.J.H.)
- The Metabolomics Innovation Centre, Edmonton, AB T6G 2N4, Canada
| | - David Bénimélis
- UPR Chrome, University Nimes, CEDEX 1, 30021 Nîmes, France; (V.T.); (D.B.); (P.M.)
| | - Bérénice Vanhoye
- UMR INRAE 1158 Transfrontalière BioEcoAgro, BIOlogie des Plantes et Innovation (BIOPI), UPJV, UFR de Pharmacie, 80037 Amiens, France; (R.M.); (B.V.)
| | | | - Muriel Sylvestre
- COVACHIM-M2E Laboratory EA 3592, Department of Chemistry, UFR SEN, Fouillole Campus, University of Antilles, CEDEX, 97110 Pointe-à-Pitre, France;
| | - Yvens Cheremond
- URE, Université d’État d’Haïti, Port-au-Prince HT6110, Haiti;
| | - Patrick Meffre
- UPR Chrome, University Nimes, CEDEX 1, 30021 Nîmes, France; (V.T.); (D.B.); (P.M.)
| | - Gerardo Cebrián-Torrejón
- COVACHIM-M2E Laboratory EA 3592, Department of Chemistry, UFR SEN, Fouillole Campus, University of Antilles, CEDEX, 97110 Pointe-à-Pitre, France;
| | - Zohra Benfodda
- UPR Chrome, University Nimes, CEDEX 1, 30021 Nîmes, France; (V.T.); (D.B.); (P.M.)
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Chen L, Kumar S, Wu H. A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance. Arch Microbiol 2023; 205:356. [PMID: 37863957 DOI: 10.1007/s00203-023-03699-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/25/2023] [Accepted: 10/03/2023] [Indexed: 10/22/2023]
Abstract
The emergence and transmission of antibiotic resistance is a global public health crisis with significant burden on healthcare systems, resulting in high mortality and economic costs. In 2019, almost five million deaths were associated with drug-resistant infections, and if left unchecked, the global economy could lose $100 trillion by 2050. To effectively combat this crisis, it is essential for all countries to understand the current situation of antibiotic resistance. In this review, we examine the current driving factors leading to the crisis, impact of critical superbugs in three regions, and identify novel mechanisms of antibiotic resistance. It is crucial to monitor the phenotypic characteristics of drug-resistant pathogens and describe the mechanisms involved in preventing the emergence of cross-resistance to novel antimicrobials. Additionally, maintaining an active pipeline of new antibiotics is essential for fighting against diverse antibiotic-resistant pathogens. Developing antibacterial agents with novel mechanisms of action is a promising way to combat increasing antibiotic-resistant pathogens.
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Affiliation(s)
- Lei Chen
- Jiangsu Vocational College of Medicine, Yancheng, China
- School of Graduate Studies, Management and Science University, Shah Alam, Malaysia
| | - Suresh Kumar
- Faculty of Health and Life Sciences, Management and Science University, Shah Alam, Malaysia.
| | - Hongyan Wu
- Jiangsu Vocational College of Medicine, Yancheng, China
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9
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Maina JW, Onyambu FG, Kibet PS, Musyoki AM. Multidrug-resistant Gram-negative bacterial infections and associated factors in a Kenyan intensive care unit: a cross-sectional study. Ann Clin Microbiol Antimicrob 2023; 22:85. [PMID: 37710247 PMCID: PMC10500940 DOI: 10.1186/s12941-023-00636-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 08/29/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND Patients admitted to intensive care units (ICU) are at risk of Gram-negative bacteria (GNB) infections, especially those caused by multidrug-resistant (MDR) isolates, increasing morbidity, mortality, and healthcare costs. However, epidemiological surveillance data on MDR bacteria to inform infection prevention and control (IPCs) interventions is limited in our study setting. Here we assessed the prevalence and factors associated with GNB infections in ICU- patients admitted in our study setting. METHODS This was a hospital-based cross-sectional study among patients admitted to ICU at the Nairobi West Hospital, Kenya, between January and October 2022. Altogether, we recruited 162 patients, excluding those hospitalized for less than 48 h and declining consent, and collected demographics and clinical data by case report form. Blood, wound and throat swab, ascetic tap, stool, urine, tracheal aspirate, and sputum samples were collected cultured. Isolates identity and antimicrobial susceptibility were elucidated using the BD Phoenix system. RESULTS The prevalence of GNB infections was 55.6%, predominated by urinary tract infections (UTIs). We recovered 13 GNB types, with Escherichia coli (33.3%) and Klebsiella pneumoniae (31.1%) as the most common isolates. Factors associated with GNB infections were a history of antibiotic use (aOR = 4.23, p = 0.001), nasogastric tube use (NGT, aOR = 3.04, p = 0.013), respiratory tract (RT, aOR = 5.3, p = 0.005) and cardiovascular (CV, aOR = 5.7, p = 0.024) conditions. 92% of the isolates were MDR,predominantly Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. CONCLUSION We report a high prevalence of MDR-GNB infections, predominated by UTI, in ICU, whereby patients with a history of antibiotic use, using the NGT, and having RT and CV conditions were at increased risk. To improve the management of ICU-admitted patients, continuous education, training, monitoring, evaluation and feedback on infection prevention and control are warranted in our study setting.
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Affiliation(s)
- Jane Wairimu Maina
- Department of Medical Laboratory Science, The Nairobi West Hospital, Nairobi, Kenya.
- Department of Medical Laboratory Science, Kenyatta University, Nairobi, Kenya.
| | | | - Peter Shikuku Kibet
- Department of Medical Laboratory Science, The Nairobi West Hospital, Nairobi, Kenya
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10
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Puan SL, Erriah P, Baharudin MMAA, Yahaya NM, Kamil WNIWA, Ali MSM, Ahmad SA, Oslan SN, Lim S, Sabri S. Antimicrobial peptides from Bacillus spp. and strategies to enhance their yield. Appl Microbiol Biotechnol 2023; 107:5569-5593. [PMID: 37450018 DOI: 10.1007/s00253-023-12651-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/13/2023] [Accepted: 06/16/2023] [Indexed: 07/18/2023]
Abstract
Antibiotic resistance is a growing concern that is affecting public health globally. The search for alternative antimicrobial agents has become increasingly important. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this review, we provide an overview of Bacillus-derived AMPs, including their classification into ribosomal (bacteriocins) and non-ribosomal peptides (lipopeptides and polyketides). Additionally, we delve into the molecular mechanisms of AMP production and describe the key biosynthetic gene clusters involved. Despite their potential, the low yield of AMPs produced under normal laboratory conditions remains a challenge to large-scale production. This review thus concludes with a comprehensive summary of recent studies aimed at enhancing the productivity of Bacillus-derived AMPs. In addition to medium optimization and genetic manipulation, various molecular strategies have been explored to increase the production of recombinant antimicrobial peptides (AMPs). These include the selection of appropriate expression systems, the engineering of expression promoters, and metabolic engineering. Bacillus-derived AMPs offer great potential as alternative antimicrobial agents, and this review provides valuable insights on the strategies to enhance their production yield, which may have significant implications for combating antibiotic resistance. KEY POINTS: • Bacillus-derived AMP is a potential alternative therapy for resistant pathogens • Bacillus produces two main classes of AMPs: ribosomal and non-ribosomal peptides • AMP yield can be enhanced using culture optimization and molecular approaches.
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Affiliation(s)
- Sheau Ling Puan
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Pirasannah Erriah
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Mohamad Malik Al-Adil Baharudin
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Normi Mohd Yahaya
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Wan Nur Ismah Wan Ahmad Kamil
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Mohd Shukuri Mohamad Ali
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
- Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Siti Aqlima Ahmad
- Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Siti Nurbaya Oslan
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
- Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia
| | - Sooa Lim
- Department of Pharmaceutical Engineering, Hoseo University, 31499, Asan-Si, Chungnam, Republic of Korea
| | - Suriana Sabri
- Enzyme and Microbial Technology Research Centre, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia.
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia.
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11
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Sharma K, Pandey S, Sekar H, Alan T, Gundabala V. Microfluidics Based Generation of Curcumin Loaded Microfibrous Mat against Staphylococcus aureus Biofilm by Photodynamic Therapy. ACS APPLIED BIO MATERIALS 2023; 6:1092-1104. [PMID: 36780700 DOI: 10.1021/acsabm.2c00971] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Abstract
The rapid increase in multidrug resistant biofilm infections is a major concern for global health. A highly effective therapy is required for the treatment of biofilm related infections. In this study, curcumin loaded alginate microfibers were generated by using the microfluidic technique. In this strategy, alginate microfibers are used as a carrier for the encapsulation of curcumin and then are irradiated with blue light to assess the efficacy of a combined therapy (blue light + curcumin) against drug resistant Staphylococcus aureus (S. aureus). The advantage of utilizing photodynamic therapy (PDT) is the usage of a non-antibiotic mode to inactivate bacterial cells. In the presence of blue light, the curcumin loaded alginate microfibers have shown good eradication activity against biofilms formed by multidrug resistant S. aureus. We achieved different diameters of curcumin loaded alginate microfibers through manipulation of flow rates. The curcumin loaded microfibers were characterized for their size, morphology, and curcumin encapsulation. Further, the efficacy of these microfibers in the presence of blue light has been evaluated against biofilm forming S. aureus (NCIM 5718) through optical and electron microscopy. This study employs microfluidic techniques to obtain an efficacious and cost-effective microfibrous scaffold for controlled release of curcumin to treat biofilms in the presence of blue light.
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Affiliation(s)
- Kajal Sharma
- Department of Chemical Engineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai 400076, India
- Department of Mechanical and Aerospace Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Shipra Pandey
- Department of Chemical Engineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai 400076, India
| | - Hariharan Sekar
- Department of Chemical Engineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai 400076, India
| | - Tuncay Alan
- Department of Mechanical and Aerospace Engineering, Monash University, Clayton, Victoria 3800, Australia
| | - Venkat Gundabala
- Department of Chemical Engineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai 400076, India
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12
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Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling. Pathogens 2023; 12:pathogens12030449. [PMID: 36986372 PMCID: PMC10058483 DOI: 10.3390/pathogens12030449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/13/2023] [Accepted: 03/10/2023] [Indexed: 03/18/2023] Open
Abstract
Natural products have important pharmacological activities. This study sought to investigate the activity of the compound betulinic acid (BA) against different strains of bacteria and fungi. The minimum inhibitory concentration (MIC) was determined and then the minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). After performing the in vitro tests, molecular modeling studies were carried out to investigate the mechanism of action of BA against the selected microorganisms. The results showed that BA inhibited the growth of microbial species. Among the 12 species (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Mycobacterium tuberculosis, Candida albicans, C. tropicalis, C. glabrata, Aspergillus flavus, Penicillium citrinum, Trichophyton rubrum, and Microsporum canis) investigated, 9 (75%) inhibited growth at a concentration of 561 µM and 1 at a concentration of 100 µM. In general, the MBC and MFC of the products were between 561 and 1122 μM. In silico studies showed that BA presented a mechanism of action against DNA gyrase and beta-lactamase targets for most of the bacteria investigated, while for fungi the mechanism of action was against sterol 14α-demethylase (CYP51) targets and dihydrofolate reductase (DHFR). We suggest that BA has antimicrobial activity against several species.
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G K, Vasudevan K, Dey H, Kausar T, Udhaya Kumar S, Thirumal Kumar D, Zayed H, George Priya Doss C. Elucidating the mechanism of antimicrobial resistance in Mycobacterium tuberculosis using gene interaction networks. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 134:53-74. [PMID: 36858742 DOI: 10.1016/bs.apcsb.2022.11.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Antimicrobial resistance (AMR) in microorganisms is an urgent global health threat. AMR of Mycobacterium tuberculosis is associated with significant morbidity and mortality. It is of great importance to underpin the resistance pathways involved in the mechanisms of AMR and identify the genes that are directly involved in AMR. The focus of the current study was the bacteria M. tuberculosis, which carries AMR genes that give resistance that lead to multidrug resistance. We, therefore, built a network of 43 genes and examined for potential gene-gene interactions. Then we performed a clustering analysis and identified three closely related clusters that could be involved in multidrug resistance mechanisms. Through the bioinformatics pipeline, we consistently identified six-hub genes (dnaN, polA, ftsZ, alr, ftsQ, and murC) that demonstrated the highest number of interactions within the clustering analysis. This study sheds light on the multidrug resistance of MTB and provides a protocol for discovering genes that might be involved in multidrug resistance, which will improve the treatment of resistant strains of TB.
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Affiliation(s)
- Keerthana G
- Department of Biotechnology, School of Applied Sciences, REVA University, Bengaluru, India; Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India; Faculty of Allied Health Sciences, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, India; Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha, Qatar
| | - Karthick Vasudevan
- Department of Biotechnology, School of Applied Sciences, REVA University, Bengaluru, India.
| | - Hrituraj Dey
- Department of Biotechnology, School of Applied Sciences, REVA University, Bengaluru, India
| | - Tasmia Kausar
- Department of Biotechnology, School of Applied Sciences, REVA University, Bengaluru, India
| | - S Udhaya Kumar
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
| | - D Thirumal Kumar
- Faculty of Allied Health Sciences, Meenakshi Academy of Higher Education and Research (Deemed to be University), Chennai, India
| | - Hatem Zayed
- Department of Biomedical Sciences, College of Health and Sciences, QU Health, Qatar University, Doha, Qatar
| | - C George Priya Doss
- Laboratory of Integrative Genomics, Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
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14
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Kusuma IY, Matuz M, Bordás R, Juhasz Haverinen M, Bahar MA, Hajdu E, Visnyovszki Á, Ruzsa R, Doró P, Engi Z, Csupor D, Benko R. Antibiotic use in elderly patients in ambulatory care: A comparison between Hungary and Sweden. Front Pharmacol 2022; 13:1042418. [PMID: 36467037 PMCID: PMC9714540 DOI: 10.3389/fphar.2022.1042418] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/27/2022] [Indexed: 11/23/2023] Open
Abstract
Background: The elderly use antibiotics frequently due to their increasing infection susceptibility. Given the high and increasing proportion of elderly in the population, their antibiotic use is substantial. Objective: This study aimed to compare antibiotic use in the elderly in the ambulatory care sector between Hungary and Sweden. Methods: This retrospective, descriptive, cross-national, comparative study included antibacterial use data from the Hungarian National Health Insurance Fund and the Swedish eHealth Agency. Antibiotic use (anatomical therapeutical chemical: J01) was expressed as the number of prescriptions/1000 inhabitants/year or month and was further stratified by age and sex. Results: Antibiotic exposure was higher in the Hungarian elderly population (649.8 prescriptions/1000 inhabitants/year) compared to its Swedish counterparts (545.0 prescriptions/1000 inhabitants/year). Hungary had a similar scale of antibacterial exposure across all elderly age subgroups, with different trends in males and females, while Sweden had a stepwise increase in antibiotic exposure by age in both sexes. The seasonal fluctuation was high in Hungary and reached a peak of 80.7 prescriptions/1000 inhabitants/month in January 2017, while even antibiotic use was detected throughout the year in Sweden. The pattern of antibiotic use in the elderly considerably differed between the two countries. Penicillin and beta-lactamase combinations, such as co-amoxiclav, were more frequently used in Hungary than in Sweden (19.08% vs 1.83% of corresponding total ambulatory antibiotic use). Likewise, quinolones were more commonly used in Hungary than in Sweden (34.53% vs. 9.98). The elderly in Sweden were mostly prescribed narrow spectra penicillins (26.71% vs. 0.29% in Hungary). Conclusion: This cross-national comparison revealed important differences in all aspects of antibiotic use in the elderly between the two countries. The identical scale and pattern of antibiotic use cannot be anticipated due to the poorer health status of the Hungarian elderly population. However, the substantial differences indicate some room for improvement in the antibiotic prescription for the Hungarian elderly.
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Affiliation(s)
- Ikhwan Yuda Kusuma
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Pharmacy Study Program, Universitas Harapan Bangsa, Purwokerto, Indonesia
| | - Maria Matuz
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Albert Szent-Györgyi Health Centre, Central Pharmacy, University of Szeged, Szeged, Hungary
| | - Réka Bordás
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | | | - Muh. Akbar Bahar
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Department of Pharmacy, Faculty of Pharmacy, Universitas Hasanuddin, Makassar, Indonesia
| | - Edit Hajdu
- Albert Szent-Györgyi Health Centre, Department of Internal Medicine Infectiology Unit, University of Szeged, Szeged, Hungary
| | - Ádám Visnyovszki
- Albert Szent-Györgyi Health Centre, Department of Internal Medicine Infectiology Unit, University of Szeged, Szeged, Hungary
| | - Roxána Ruzsa
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | - Péter Doró
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | - Zsófi Engi
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
| | - Dezső Csupor
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Ria Benko
- Institute of Clinical Pharmacy, University of Szeged, Szeged, Hungary
- Albert Szent-Györgyi Health Centre, Central Pharmacy, University of Szeged, Szeged, Hungary
- Albert Szent-Györgyi Health Centre, Emergency Department, University of Szeged, Szeged, Hungary
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15
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Levi G, Lurie-Weinberger M, Keren-Paz A, Andremont AO, Schwartz D, Carmeli Y. Unraveling the Diversity of Co-Colonization by CPE. Microorganisms 2022; 10:1292. [PMID: 35889010 PMCID: PMC9316973 DOI: 10.3390/microorganisms10071292] [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: 05/31/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 02/04/2023] Open
Abstract
Antibiotic-resistant bacteria, and more specifically, carbapenem-producing Enterobacterales (CPE) strains, are increasing worldwide. Despite their growing prevalence, in most high-income countries, the detection of CPE is still considered a low-frequency event. Sporadically, patients co-colonized with distinct CPE strains and/or different carbapenemase enzymes are detected. In this paper, we present three cases that illustrate the underlying mechanisms of co-colonization, focusing on horizontal gene transfer (HGT) and patient-to-patient transmission. We also demonstrate the diversity of CPE species and discuss the potential consequences of co-colonization.
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Affiliation(s)
- Gabrielle Levi
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv 6423906, Israel; (G.L.); (M.L.-W.); (A.K.-P.); (D.S.)
| | - Mor Lurie-Weinberger
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv 6423906, Israel; (G.L.); (M.L.-W.); (A.K.-P.); (D.S.)
| | - Alona Keren-Paz
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv 6423906, Israel; (G.L.); (M.L.-W.); (A.K.-P.); (D.S.)
| | - Antoine O. Andremont
- Microbiology Department, Université Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France;
| | - David Schwartz
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv 6423906, Israel; (G.L.); (M.L.-W.); (A.K.-P.); (D.S.)
| | - Yehuda Carmeli
- National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel Aviv 6423906, Israel; (G.L.); (M.L.-W.); (A.K.-P.); (D.S.)
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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16
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Paruch K, Biernasiuk A, Khylyuk D, Paduch R, Wujec M, Popiołek Ł. Synthesis, Biological Activity and Molecular Docking Studies of Novel Nicotinic Acid Derivatives. Int J Mol Sci 2022; 23:2823. [PMID: 35269966 PMCID: PMC8911400 DOI: 10.3390/ijms23052823] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 11/16/2022] Open
Abstract
In our research, we used nicotinic acid as a starting compound, which was subjected to a series of condensation reactions with appropriate aldehydes. As a result of these reactions, we were able to obtain a series of twelve acylhydrazones, two of which showed promising activity against Gram-positive bacteria (MIC = 1.95-15.62 µg/mL), especially against Staphylococcus epidermidis ATCC 12228 (MIC = 1.95 µg/mL). Moreover, the activity of compound 13 against the Staphylococcus aureus ATCC 43300 strain, i.e., the MRSA strain, was MIC = 7.81 µg/mL. Then, we subjected the entire series of acylhydrazones to a cyclization reaction in the acetic anhydride, thanks to which we were able to obtain twelve new 3-acetyl-2,5-disubstituted-1,3,4-oxadiazoline derivatives. Obtained 1,3,4-oxadiazolines were also tested for antimicrobial activity. The results showed high activity of compound 25 with a 5-nitrofuran substituent, which was active against all tested strains. The most promising activity of this compound was found against Gram-positive bacteria, in particular against Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538 (MIC = 7.81 µg/mL) and ATCC 43300 MRSA strains (MIC = 15.62 µg/mL). Importantly, the best performing compounds did not show cytotoxicity against normal cell lines. It seems practical to use some of these compounds or their derivatives in the future in the prevention and treatment of infections caused by some pathogenic or opportunistic microorganisms.
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Affiliation(s)
- Kinga Paruch
- Chair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland; (D.K.); (M.W.); (Ł.P.)
| | - Anna Biernasiuk
- Chair and Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland;
| | - Dmytro Khylyuk
- Chair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland; (D.K.); (M.W.); (Ł.P.)
| | - Roman Paduch
- Department of Virology and Immunology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, 19 Akademicka Street, 20-033 Lublin, Poland;
| | - Monika Wujec
- Chair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland; (D.K.); (M.W.); (Ł.P.)
| | - Łukasz Popiołek
- Chair and Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland; (D.K.); (M.W.); (Ł.P.)
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17
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Biological Activity, Lipophilicity and Cytotoxicity of Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines. Int J Mol Sci 2021; 22:ijms222413669. [PMID: 34948461 PMCID: PMC8704594 DOI: 10.3390/ijms222413669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 01/21/2023] Open
Abstract
Antibiotic resistance is now a global problem, and the lack of effective antimicrobial agents for the treatment of diseases caused by resistant microbes is increasing. The 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines presented in this article may provide a good starting point for the development of potential new effective antimicrobial agents useful in the treatment of bacterial and fungal infections. Particular attention is drawn to the 1,3,4-oxadiazole derivative marked with the number 29 with 5-nitrofuran-2-yl substituent in its chemical structure. This substance showed a strong bactericidal effect, especially against Staphylococcus spp., and no cytotoxicity to the L929 normal cell line.
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18
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Bekiaridou A, Karlafti E, Oikonomou IM, Ioannidis A, Papavramidis TS. Probiotics and Their Effect on Surgical Wound Healing: A Systematic Review and New Insights into the Role of Nanotechnology. Nutrients 2021; 13:nu13124265. [PMID: 34959817 PMCID: PMC8704946 DOI: 10.3390/nu13124265] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/21/2021] [Accepted: 11/26/2021] [Indexed: 11/17/2022] Open
Abstract
Skin tissue repair is of fundamental importance for maintaining homeostasis regulation, protection barrier, absorption, and excretion of skin tissue. Wound healing is a complicated process that can be impaired by infections and therefore have a significant economic and social impact. Simultaneously, the overuse of antibiotics has led to antimicrobial resistance and loss of their efficacy. Thus, the need for alternative antimicrobial agents is urgent. The newest approaches on wound dressings employ new therapeutic agents, such as probiotics. Probiotics alone or in tandem with nanotechnology-based techniques exhibit a broad range of benefits on surgical wounds. This systematic review aims to consider current knowledge of probiotic effects on animals and humans regarding surgical wound healing and provide new insights into the role of nanotechnology. The databases included were PubMed (MEDLINE), Scopus, and Cochrane Library (CENTRAL). Studies focused on burns, chronic wounds, and diabetic ulcers were excluded. The promising industry of probiotics demonstrates a significant upsurge as more and more healthy individuals rely their well-being on alternative medicine. Included probiotics illustrated positive results on wound re-epithelization, neovascularization, and wound healing. No adverse effects were noted.
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Affiliation(s)
- Alexandra Bekiaridou
- 1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece; (A.B.); (E.K.); (I.M.O.)
| | - Eleni Karlafti
- 1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece; (A.B.); (E.K.); (I.M.O.)
| | - Ilias Marios Oikonomou
- 1st Propaedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece; (A.B.); (E.K.); (I.M.O.)
| | - Aristidis Ioannidis
- 1st Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki (AUTH), 54621 Thessaloniki, Greece;
| | - Theodossis S. Papavramidis
- 1st Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki (AUTH), 54621 Thessaloniki, Greece;
- Correspondence: ; Fax: +30-231-042-0293
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19
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Maleki A, Taheri-Ledari R, Eivazzadeh-Keihan R, de la Guardia M, Mokhtarzadeh A. Preparation of Carbon-14 Labeled 2-(2-mercaptoacetamido)-3-phenylpropanoic Acid as Metallo-beta-lactamases Inhibitor (MBLI), for Coadministration with Beta-lactam Antibiotics. Curr Org Synth 2019; 16:765-771. [DOI: 10.2174/1570179416666190423114704] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Revised: 02/08/2019] [Accepted: 03/11/2019] [Indexed: 01/21/2023]
Abstract
Aim and Objective:
Bacteria could become resistant to β-lactam antibiotics through production of β-
lactamase enzymes like metallo-β-lactamase. 2-(2-mercaptoacetamido)-3-phenylpropanoic acid was reported
as a model inhibitor for this enzyme. In order to elucidate the mechanism of action in the body’s internal
environment, preparation of a labeled version of 2-(2-mercaptoacetamido)-3-phenylpropanoic acid finds
importance. In this regard, we report a convenient synthetic pathway for preparation of carbon-14 labeled 2-(2-
mercaptoacetamido)-3-phenylpropanoic acid.
Materials and Methods:
This study was initiated by using non-radioactive materials. Then, necessary
characterization was performed after each of the reactions. Finally, the synthesis steps were continued to
produce the target labeled product. For labeled products, the process was started from benzoic acid-[carboxyl-
14C] which has been prepared from barium 14C-carbonate. Chromatography column and NMR spectroscopy
were used for purifications and identification of desired products, respectively. Barium [14C]carbonate was
purchased from Amersham Pharmacia Biotech and was converted to [14C]benzyl bromide. Radioactivity was
determined using liquid scintillation spectrometer.
Results:
We used [14C]PhCH2Br which was previously prepared from [14C]BaCO3, H2SO4, PhMgI, LAH and
HBr, respectively. To neutralize the [14C]phenylalanine in acidic condition and to reach an isoelectric point of
phenylalanine (pH = 5.48), Pb(OH)2 was used. Next, thioacetic acid and bromo acetic acid were used to
prepare (acetylthio) acetic acid. A peptide coupling reagent was used in this stage to facilitating amide bond
formation reaction between [14C]methyl-2-amino-3-phenyl propanoate hydrochloride and (acetylthio) acetic
acid.
Conclusion:
Carbon-14 labeled 2-(2-mercaptoacetamido)-3-phenylpropanoic acid via radioactive
phenylalanine was obtained with overall chemical yield 73% and radioactivity 65.3 nCi. The labeled target
product will be used for in vivo pharmacological studies.
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Affiliation(s)
- Ali Maleki
- Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
| | - Reza Taheri-Ledari
- Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
| | - Reza Eivazzadeh-Keihan
- Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
| | - Miguel de la Guardia
- Department of Analytical Chemistry, University of Valencia, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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20
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Chopade SS, Dhaneshwar SS. Determination of the mitigating effect of colon-specific bioreversible codrugs of mycophenolic acid and aminosugars in an experimental colitis model in Wistar rats. World J Gastroenterol 2018; 24:1093-1106. [PMID: 29563754 PMCID: PMC5850129 DOI: 10.3748/wjg.v24.i10.1093] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 12/31/2017] [Accepted: 01/23/2018] [Indexed: 02/07/2023] Open
Abstract
AIM To design colon-targeted codrugs of mycophenolic acid (MPA) and aminosugars as a safer option to mycophenolate mofetil (MMF) in the management of inflammatory bowel disease.
METHODS Codrugs were synthesized by coupling MPA with aminosugars (D-glucosamine and D-galactosamine) using EDCI coupling. The structures were confirmed by infrared radiation, nuclear magnetic resonance, mass spectroscopy and elemental analysis. The release profile of codrugs was extensively studied in aqueous buffers, upper gastrointestinal homogenates, faecal matter and caecal homogenates (in vitro) and rat blood (in vitro). Anti-colitic activity was assessed in 2,4,6-trinitrobezenesulfonic acid-induced colitis in Wistar rats by the estimation of various demarcating parameters. Statistical evaluation was performed by applying one-way and two-way ANOVA when compared with the disease control.
RESULTS The prodrugs resisted activation in HCl buffer (pH 1.2) and stomach homogenates of rats with negligible hydrolysis in phosphate buffer (pH 7.4) and intestinal homogenates. Incubation with colon homogenates (in vitro) produced 76% to 89% release of MPA emphasizing colon-specific activation of codrugs and the release of MPA and aminosugars at the site of action. In the in vitro studies, the prodrug of MPA with D-glucosamine (MGLS) was selected which resulted in 68% release of MPA in blood. in vitro studies on MGLS revealed its colon-specific activation after a lag time of 8 h which could be ascribed to the hydrolytic action of N-acyl amidases found in the colon. The synthesized codrugs markedly diminished disease activity score and revived the disrupted architecture of the colon that was comparable to MMF but superior to MPA.
CONCLUSION The significant attenuating effect of prodrugs and individual aminosugars on colonic inflammation proved that the rationale of the codrug approach is valid.
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Affiliation(s)
- Shakuntala Santosh Chopade
- Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune 411038, India
| | - Suneela Sunil Dhaneshwar
- Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune 411038, India
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Ractliffe LH, Guevara-Pozo D, Lopez-Roman R. In vitro maintenance of Fasciola hepatica: a factorial approach based on egg production. Exp Parasitol 1969; 26:41-51. [PMID: 5362314 DOI: 10.1016/0014-4894(69)90093-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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