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Taylor M, Griffin RL, Walker J, James C, Akinsanya A, Duncan M, Lee RA. Use of standardized nasal and skin decolonization to reduce rates of bacteremia in patients undergoing extracorporeal membrane oxygenation. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2025; 5:e41. [PMID: 39949999 PMCID: PMC11822575 DOI: 10.1017/ash.2025.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/15/2024] [Accepted: 12/17/2024] [Indexed: 02/16/2025]
Abstract
Objective We aimed to determine if implementation of universal nasal decolonization with daily chlorhexidine bathing will decrease blood stream infections (BSI) in patients undergoing extracorporeal membrane oxygenation (ECMO). Design Retrospective cohort study. Setting Tertiary care facility. Patients Patients placed on ECMO from January 1, 2017 to December 31, 2023. Intervention Daily bathing with 4% chlorhexidine soap and universal mupirocin nasal decolonization were initiated for all ECMO patients May 2021. The primary outcome was rate of ECMO-attributable positive blood cultures. Zero-inflated Poisson regression analysis was performed to estimate rate ratios (RRs) for the association between decolonization with BSI rates. Results A total of 776 patients met inclusion criteria during the study period, 425 (55%) preimplementation and 351 (45%) post-implementation. Following implementation of decolonization, the overall incidence rate of BSI increased nonsignificantly from 10.7 to 14.0 infections per 1000 ECMO days (aRR 1.09, 95% CI 0.74-1.59). For gram-positive cocci (GPC) pathogens, a nonsignificant 40% increased rate was observed in the post-implementation period (RR 1.40, 95% CI 0.89-2.21), due mostly to a significant increase in the crude rate of Enterococcus BSI (RR 1.89, 95% CI 1.01-3.55). Excluding Enterococcus resulted in a nonsignificant 28% decreased rate (aRR 0.72, 95% CI 0.39-1.36) due to a nonsignificant 55% decreased rate of MRSA (aRR 0.45, 95% CI 0.18-3.58). Conclusions Implementation of a universal decolonization protocol did not significantly reduce rates of certain BSIs, including MRSA and other gram-positive pathogens. Although nonsignificant, reduction in BSI rates in this patient population has important implications on surveillance metrics, such as MRSA, and in the future, hospital-onset bacteremia.
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Affiliation(s)
- Madyson Taylor
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Russell L Griffin
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, ALUSA
| | - Jeremey Walker
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Catina James
- Department of Infection Prevention, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Angela Akinsanya
- Department of Infection Prevention, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Mary Duncan
- Department of Infection Prevention, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rachael A Lee
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Kuznetsova MV, Nesterova LY, Mihailovskaya VS, Selivanova PA, Kochergina DA, Karipova MO, Valtsifer IV, Averkina AS, Starčič Erjavec M. Nosocomial Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus: Sensitivity to Chlorhexidine-Based Biocides and Prevalence of Efflux Pump Genes. Int J Mol Sci 2025; 26:355. [PMID: 39796210 PMCID: PMC11721292 DOI: 10.3390/ijms26010355] [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: 12/06/2024] [Revised: 12/30/2024] [Accepted: 12/31/2024] [Indexed: 01/13/2025] Open
Abstract
The widespread use of disinfectants and antiseptics has led to the emergence of nosocomial pathogens that are less sensitive to these agents, which in combination with multidrug resistance (MDR) can pose a significant epidemiologic risk. We investigated the susceptibility of nosocomial Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus to a 0.05% chlorhexidine (CHX) solution and a biocidal S7 composite solution based on CHX (0.07%) and benzalkonium chloride (BAC, 0.055%). The prevalence of efflux pump genes associated with biocide resistance and their relationship to antibiotic resistance was also determined. Both biocides were more effective against Gram-positive S. aureus than Gram-negative bacteria. The most resistant strains were P. aeruginosa strains, which were mainly killed by 0.0016% CHX and by 0.0000084% (CHX)/0.0000066% (BAC) S7. The S7 bactericidal effect was observed on P. aeruginosa and S. aureus after 10 min, while the bactericidal effect of CHX was only observed after 30 min. qacEΔ1 and qacE efflux pump genes were prevalent among E. coli and K. pneumoniae, while mexB was more often detected in P. aeruginosa. norA, norB, mepA, mdeA, and sepA were prevalent in S. aureus. The observed prevalence of efflux pump genes highlights the potential problem whereby the sensitivity of bacteria to biocides could decline rapidly in the future.
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Affiliation(s)
- Marina V. Kuznetsova
- Laboratory of Molecular Biotechnology, Institute of Ecology and Genetics of Microorganisms Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614081 Perm, Russia; (M.V.K.); (V.S.M.); (P.A.S.); (D.A.K.)
- Department of Microbiology and Virology, Perm State Medical University Named After Academician E. A. Wagner, 614000 Perm, Russia;
| | - Larisa Y. Nesterova
- Laboratory of Microorganisms’ Adaptation, Institute of Ecology and Genetics of Microorganisms Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614081 Perm, Russia;
| | - Veronika S. Mihailovskaya
- Laboratory of Molecular Biotechnology, Institute of Ecology and Genetics of Microorganisms Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614081 Perm, Russia; (M.V.K.); (V.S.M.); (P.A.S.); (D.A.K.)
| | - Polina A. Selivanova
- Laboratory of Molecular Biotechnology, Institute of Ecology and Genetics of Microorganisms Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614081 Perm, Russia; (M.V.K.); (V.S.M.); (P.A.S.); (D.A.K.)
| | - Darja A. Kochergina
- Laboratory of Molecular Biotechnology, Institute of Ecology and Genetics of Microorganisms Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614081 Perm, Russia; (M.V.K.); (V.S.M.); (P.A.S.); (D.A.K.)
| | - Marina O. Karipova
- Department of Microbiology and Virology, Perm State Medical University Named After Academician E. A. Wagner, 614000 Perm, Russia;
| | - Igor V. Valtsifer
- Department of Multiphase Dispersed System, Institute of Technical Chemistry Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614013 Perm, Russia; (I.V.V.); (A.S.A.)
| | - Anastasia S. Averkina
- Department of Multiphase Dispersed System, Institute of Technical Chemistry Ural Branch Russian Academy of Sciences, Perm Federal Research Centre of Ural Branch of RAS, 614013 Perm, Russia; (I.V.V.); (A.S.A.)
| | - Marjanca Starčič Erjavec
- Department of Microbiology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
- Department of Biology, Faculty of Natural Sciences and Mathematics, University of Maribor, 2000 Maribor, Slovenia
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Zhang J, Cheng L, Li H, Chen X, Zhang L, Shan T, Wang J, Chen D, Shen J, Zhou X, Gou L, Zhang L, Zhou X, Ren B. Challenges of quaternary ammonium antimicrobial agents: Mechanisms, resistance, persistence and impacts on the microecology. THE SCIENCE OF THE TOTAL ENVIRONMENT 2025; 958:178020. [PMID: 39689472 DOI: 10.1016/j.scitotenv.2024.178020] [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: 09/24/2024] [Revised: 12/07/2024] [Accepted: 12/07/2024] [Indexed: 12/19/2024]
Abstract
Quaternary ammonium compounds (QACs) served as broad spectrum antimicrobial agents are widely applied for surface disinfection, skin and mucous disinfection, and mouthwash. The daily applications of QACs have significantly increased, especially during the COVID-19 pandemic. However, the environmental residues of QACs have demonstrated harmful impacts on the environment, leading to an increase in environmental contamination, resistant microbes and disruption of microecology. The actions of QACs were related to their cationic character, which can impact the negatively charged cell membranes, but the details are still unclear. Moreover, bacteria with lower sensitivity and resistant pathogens have been detected in clinics and environments, while QACs were also reported to induce the formation of bacterial persisters. Even worse, the resistant bacteria even showed co-resistance and cross-resistance with traditional antibiotics, decreasing therapeutic effectiveness, and disrupting the microecology homeostasis. Unfortunately, the resistance and persistence mechanisms of QACs and the effects of QACs on microecology are still not clear, which even neglected during their daily usages. Therefore, we summarized and discussed current understandings on the antimicrobial actions, resistance, persistence and impacts on the microecology to highlight the challenges in the QACs applications and discuss the possible strategies for overcoming their drawbacks.
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Affiliation(s)
- Jiaxin Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Hao Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, 500 Quxi Road, Shanghai 200011, China; National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, No. 639, Zhizaoju Road, Shanghai 200011, China
| | - Xi Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lin Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Tiantian Shan
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China; Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jiannan Wang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Ding Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jiawei Shen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Xinxuan Zhou
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lichen Gou
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Lixin Zhang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Biao Ren
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
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Chatzigiannidou I, Heyse J, Props R, Rubbens P, Mermans F, Teughels W, Van de Wiele T, Boon N. Real-time flow cytometry to assess qualitative and quantitative responses of oral pathobionts during exposure to antiseptics. Microbiol Spectr 2024; 12:e0095524. [PMID: 39162497 PMCID: PMC11448261 DOI: 10.1128/spectrum.00955-24] [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: 05/03/2024] [Accepted: 07/19/2024] [Indexed: 08/21/2024] Open
Abstract
Antiseptics are widely used in oral healthcare to prevent or treat oral diseases, such as gingivitis and periodontitis. However, the incidence of bacteria being tolerant to standard antiseptics has sharply increased over the last few years. This stresses the urgency for surveillance against tolerant organisms, as well as the discovery of novel antimicrobials. Traditionally, susceptibility to antimicrobials is assessed by broth micro-dilution or disk diffusion assays, both of which are time-consuming, labor-intensive, and provide limited information on the mode of action of the antimicrobials. The abovementioned limitations highlight the need for the development of new methods to monitor and further understand antimicrobial susceptibility. In this study, we used real-time flow cytometry, combined with membrane permeability staining, as a quick and sensitive technology to study the quantitative and qualitative responses of two oral pathobionts to different concentrations of chlorhexidine (CHX), cetylpyridinium chloride (CPC), or triclosan. Apart from the real-time monitoring of cell damage, we further applied a phenotypic fingerprinting method to differentiate between the bacterial subpopulations that arose due to treatment. We quantified the pathobiont damage rate of different antiseptics at different concentrations within 15 minutes of exposure and identified the conditions under which the bacteria were most susceptible. Moreover, we detected species-specific and treatment-specific phenotypic subpopulations. This proves that real-time flow cytometry can provide information on the susceptibility of different microorganisms in a short time frame while differentiating between antiseptics and thus could be a valuable tool in the discovery of novel antimicrobial compound, while at the same time deciphering their mode of action. IMPORTANCE With increasing evidence that microorganisms are becoming more tolerant to standard antimicrobials, faster and more accessible antimicrobial susceptibility testing methods are needed. However, traditional susceptibility assays are laborious and time-consuming. To overcome the abovementioned limitations, we introduce a novel approach to define antimicrobial susceptibility in a much shorter time frame with the use of real-time flow cytometry. Furthermore, phenotypic fingerprinting analysis can be applied on the data to study the way antiseptics affect the bacterial cell morphology over time and, thus, gain information on the mode of action of a certain compound.
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Affiliation(s)
- I. Chatzigiannidou
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | | | | | | | - F. Mermans
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | - W. Teughels
- Department of Oral Health Sciences, KU Leuven, Leuven, Belgium
| | - T. Van de Wiele
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
| | - N. Boon
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
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de Oliveira LD, de Carvalho LS, Xavier ACC, de Oliveira FE, Leão MVP, Diamantino MGG, Khoury RD, Valera MC, Carvalho CAT, Abu Hasna A. In Vitro Evaluation of Sodium Hypochlorite, Chlorhexidine, Propolis, and Calcium Hydroxide Effect on Lipoteichoic-Acid-Induced Proinflammatory Cytokines Production. Dent J (Basel) 2024; 12:286. [PMID: 39329852 PMCID: PMC11431833 DOI: 10.3390/dj12090286] [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: 05/21/2024] [Revised: 08/27/2024] [Accepted: 08/30/2024] [Indexed: 09/28/2024] Open
Abstract
This study aimed to evaluate the effects of sodium hypochlorite (NaOCl), chlorhexidine (CHX), and the glycolic extract of propolis (GEP) as endodontic irrigants and of calcium hydroxide [Ca(OH)2], CHX, or Ca(OH)2 + CHX as intracanal medications on the capacity of the lipoteichoic acid (LTA) of Enterococcus faecalis in macrophages' proinflammatory cytokines production. Freshly extracted 108 human single-rooted teeth were used in this study. The LTA of E. faecalis was standardized in double-distilled pyrogen-free water (250 µg/mL) and inoculated into the specimens subdivided into nine subgroups (n = 12). Cultures of murine macrophages (RAW 264.7) were treated with 30 µL of each sample collected from root canals and incubated (37 °C, 5% CO2) for 24 h. Lastly, anti-TNF-α, anti-IL-6, anti-IP-10, anti-MIP-1α, anti-G-CSF, and anti-IL-1β DuoSet kits were used to perform an ELISA assay. Data were analyzed using one-way ANOVA and Tukey test (p ≥ 0.05). It was found that 1% NaOCl was the most effective irrigant in reducing the capacity of LTA in cytokines production, followed by 12% GEP and 2% CHX, respectively. Ca(OH)2 + CHX presented the best results when associated with NaOCl or GEP. Thus, NaOCl or GEP associated with Ca(OH)2 + CHX were effective in reducing the capacity of LTA in different macrophages pro-inflammatory cytokines production.
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Affiliation(s)
- Luciane Dias de Oliveira
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (L.D.d.O.); (L.S.d.C.); (M.V.P.L.)
| | - Lara Steffany de Carvalho
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (L.D.d.O.); (L.S.d.C.); (M.V.P.L.)
| | - Ana Claudia Carvalho Xavier
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (L.D.d.O.); (L.S.d.C.); (M.V.P.L.)
| | - Felipe Eduardo de Oliveira
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (L.D.d.O.); (L.S.d.C.); (M.V.P.L.)
| | - Mariella Vieira Pereira Leão
- Department of Bioscience and Oral Diagnosis, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (L.D.d.O.); (L.S.d.C.); (M.V.P.L.)
| | - Mariana Gadelho Gimenez Diamantino
- Department of Restorative Dentistry, Endodontics Division, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (M.G.G.D.); (R.D.K.); (M.C.V.); (C.A.T.C.)
| | - Rayana Duarte Khoury
- Department of Restorative Dentistry, Endodontics Division, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (M.G.G.D.); (R.D.K.); (M.C.V.); (C.A.T.C.)
| | - Marcia Carneiro Valera
- Department of Restorative Dentistry, Endodontics Division, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (M.G.G.D.); (R.D.K.); (M.C.V.); (C.A.T.C.)
| | - Cláudio Antonio Talge Carvalho
- Department of Restorative Dentistry, Endodontics Division, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (M.G.G.D.); (R.D.K.); (M.C.V.); (C.A.T.C.)
| | - Amjad Abu Hasna
- Department of Restorative Dentistry, Endodontics Division, Institute of Science and Technology, Campus of São José dos Campos, São Paulo State University, São Paulo 12245-000, Brazil; (M.G.G.D.); (R.D.K.); (M.C.V.); (C.A.T.C.)
- School of Dentistry, Universidad Espíritu Santo, Samborondón 092301, Ecuador
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Kadhem Z, Alkafeef S, Benov L. Singlet oxygen detection in vivo is hindered by nonspecific SOSG staining. Sci Rep 2024; 14:20669. [PMID: 39237763 PMCID: PMC11377423 DOI: 10.1038/s41598-024-71801-9] [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] [Received: 06/13/2024] [Accepted: 08/30/2024] [Indexed: 09/07/2024] Open
Abstract
Singlet oxygen is considered an important cell damaging agent due to its propensity to react with organic compounds. This drives the interest in developing methods for determination of 1O2. Simplicity of application and high sensitivity makes fluorescent probes a popular choice for in vivo 1O2 detection. Despite its proclaimed cell-impermeability, the commercially available Singlet Oxygen Sensor Green (SOSG) is widely applied to support assertions of 1O2 involvement in cell and tissue damage. Our investigation, however, demonstrate that different microbial species and cancer cells become fluorescent when exposed to SOSG under conditions which exclude generation of 1O2. Cells, permeabilized with chlorhexidine or by heat exposure under anaerobic conditions, exhibited SOSG fluorescence. Permeabilized cells could be stained with SOSG even 24 h post-permeabilization. Since SOSG is cell impermeable, the main factor that led to fluorescent staining was plasma membrane damage. Spectral analyses of different batches of SOSG revealed that SOSG endoperoxide (SOSG-EP) did not increase even after prolonged storage under the recommended conditions. The commercial preparations of SOSG, however, were not SOSG-EP free, which can produce erroneous results when SOSG staining is used as a proof of singlet oxygen production in vivo.
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Affiliation(s)
- Zainab Kadhem
- Department of Biochemistry, Faculty of Medicine, Kuwait University, 13110, Kuwait, Kuwait
| | - Selma Alkafeef
- Department of Biochemistry, Faculty of Medicine, Kuwait University, 13110, Kuwait, Kuwait
| | - Ludmil Benov
- Department of Biochemistry, Faculty of Medicine, Kuwait University, 13110, Kuwait, Kuwait.
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Kadirvelu L, Sivaramalingam SS, Jothivel D, Chithiraiselvan DD, Karaiyagowder Govindarajan D, Kandaswamy K. A review on antimicrobial strategies in mitigating biofilm-associated infections on medical implants. CURRENT RESEARCH IN MICROBIAL SCIENCES 2024; 6:100231. [PMID: 38510214 PMCID: PMC10951465 DOI: 10.1016/j.crmicr.2024.100231] [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] [Indexed: 03/22/2024] Open
Abstract
Biomedical implants are crucial in providing support and functionality to patients with missing or defective body parts. However, implants carry an inherent risk of bacterial infections that are biofilm-associated and lead to significant complications. These infections often result in implant failure, requiring replacement by surgical restoration. Given these complications, it is crucial to study the biofilm formation mechanism on various biomedical implants that will help prevent implant failures. Therefore, this comprehensive review explores various types of implants (e.g., dental implant, orthopedic implant, tracheal stent, breast implant, central venous catheter, cochlear implant, urinary catheter, intraocular lens, and heart valve) and medical devices (hemodialyzer and pacemaker) in use. In addition, the mechanism of biofilm formation on those implants, and their pathogenesis were discussed. Furthermore, this article critically reviews various approaches in combating implant-associated infections, with a special emphasis on novel non-antibiotic alternatives to mitigate biofilm infections.
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Affiliation(s)
- Lohita Kadirvelu
- Research Center for Excellence in Microscopy, Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, 641049, Tamil Nadu, India
| | - Sowmiya Sri Sivaramalingam
- Research Center for Excellence in Microscopy, Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, 641049, Tamil Nadu, India
| | - Deepsikha Jothivel
- Research Center for Excellence in Microscopy, Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, 641049, Tamil Nadu, India
| | - Dhivia Dharshika Chithiraiselvan
- Research Center for Excellence in Microscopy, Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, 641049, Tamil Nadu, India
| | | | - Kumaravel Kandaswamy
- Research Center for Excellence in Microscopy, Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, 641049, Tamil Nadu, India
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Samuels V, Mulelu AE, Ndlovu H, Marakalala MJ. Mycobacterial FtsEX-RipC interaction is required for normal growth and cell morphology in rifampicin and low ionic strength conditions. Microbiol Spectr 2024; 12:e0251523. [PMID: 38289931 PMCID: PMC10913748 DOI: 10.1128/spectrum.02515-23] [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] [Received: 06/17/2023] [Accepted: 12/23/2023] [Indexed: 02/01/2024] Open
Abstract
Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem ranking as the second leading cause of death from a single infectious agent. One of the major factors contributing toward Mtb's success as a pathogen is its unique cell wall and its ability to counteract various arms of the host's immune response. A recent genome-scale study profiled a list of candidate genes that are predicted to be essential for Mtb survival of host-mediated responses. One candidate was FtsEX, a protein complex composed of an ATP-binding domain, FtsE, and a transmembrane domain, FtsX. FtsEX functions through interaction with a periplasmic hydrolase, RipC. Homologs of FtsEX exist in other bacteria and have been linked with playing a key role in regulating peptidoglycan hydrolysis during cell elongation and division. Here, we report on Mycobacterium smegmatis, FtsE, FtsX, and RipC and their protective roles in stressful conditions. We demonstrate that the individual genes of FtsEX complex and RipC are not essential for survival in normal growth conditions but conditionally essential in low-salt media and antibiotic-treated media. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. Our results suggest that FtsE, FtsX, and RipC are required for both normal cell elongation and division and ultimately for survival in stressful conditions. IMPORTANCE Mycobacterial cell growth and division are coordinated with regulated peptidoglycan hydrolysis. Understanding cell wall gene complexes that govern normal cell division and elongation will aid in the development of tools to disarm the ability of mycobacteria to survive immune-like and antibiotic stresses. We combined genetic analyses and scanning electron microscopy to analyze morphological changes of mycobacterial FtsEX and RipC mutants in stressful conditions. We demonstrate that FtsE, FtsX, FtsEX, and RipC are conditionally required for the survival of Mycobacterium smegmatis during rifampicin treatment and in low-salt conditions. Growth defects in these conditions were characterized by short and bulgy cells as well as elongated filamentous cells. We also show that the FtsEX-RipC interaction is essential for the survival of M. smegmatis in rifampicin. Our results suggest that FtsE, FtsX, and RipC are required for normal cell wall regulation and ultimately for survival in stressful conditions.
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Affiliation(s)
- Veneshley Samuels
- Division of Medical Microbiology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Andani E. Mulelu
- Division of Medical Biochemistry and Structural Biology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Hlumani Ndlovu
- Division of Chemical Systems Biology, Department of Integrative Biomedical Sciences and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Mohlopheni J. Marakalala
- Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- Africa Health Research Institute, Durban, KwaZulu-Natal, South Africa
- Division of Infection and Immunity, University College London, London, United Kingdom
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9
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Wolden R, Ovchinnikov KV, Venter HJ, Oftedal TF, Diep DB, Cavanagh JP. The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens. Microbiol Spectr 2023; 11:e0086923. [PMID: 37905822 PMCID: PMC10715183 DOI: 10.1128/spectrum.00869-23] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 09/24/2023] [Indexed: 11/02/2023] Open
Abstract
IMPORTANCE Bacteria produce bacteriocins to inhibit growth of other bacterial species. We have studied the antimicrobial activity of a new bacteriocin produced by the skin bacterium S. haemolyticus. The bacteriocin is effective against several types of Gram-positive bacteria, including highly virulent and antibiotic-resistant strains such as Staphylococcus aureus and Enterococcus faecium. Effective antimicrobials are important for the treatment of infections and the success of major surgery and chemotherapy. Bacteriocins can be part of the solution to the global concern of antimicrobial resistance.
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Affiliation(s)
- Runa Wolden
- Department of Clinical Medicine, Faculty of Health Sciences, Research Group for Child and Adolescent Health, UiT The Arctic University of Norway, Tromsø, Norway
| | - Kirill V. Ovchinnikov
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), Ås, Norway
| | - Hermoine J. Venter
- Department of Clinical Medicine, Faculty of Health Sciences, Research Group for Child and Adolescent Health, UiT The Arctic University of Norway, Tromsø, Norway
| | - Thomas F. Oftedal
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), Ås, Norway
| | - Dzung B. Diep
- Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences (NMBU), Ås, Norway
| | - Jorunn Pauline Cavanagh
- Department of Clinical Medicine, Faculty of Health Sciences, Research Group for Child and Adolescent Health, UiT The Arctic University of Norway, Tromsø, Norway
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10
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Jiang Q, Deng Y, Li S, Yang D, Tao L. Sub-lethal concentrations of chlorhexidine inhibit Candida albicans growth by disrupting ROS and metal ion homeostasis. J Oral Microbiol 2023; 15:2278937. [PMID: 38415078 PMCID: PMC10898817 DOI: 10.1080/20002297.2023.2278937] [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: 10/27/2022] [Accepted: 10/31/2023] [Indexed: 02/29/2024] Open
Abstract
Candida albicans is a normal resident of the human oral cavity. It is also the most common fungal pathogen, causing various oral diseases, particularly in immunocompromised individuals. Chlorhexidine digluconate (CHG) is a broad-spectrum antimicrobial agent widely used in dental practice and has been recommended to treat oral candidiasis. However, its action mechanism against the fungal pathogen C. albicans remains poorly understood. The aim of the present study was to investigate the effect of CHG at sub-lethal concentrations against C. albicans. CHG inhibited the growth of C. albicans in a dose- and time-dependent manner. Cells treated with CHG exhibited altered membrane permeability, reduced metabolic activity, and enhanced metal ion and reactive oxygen species (ROS) accumulation. Copper-sensing transcription factor Mac1, iron-sensing transcription factors Sfu1 and Sef2, and copper transporter Ctr1 regulated intracellular metal ion and ROS homeostasis in response to CHG. Deletion of MAC1, SFU1, or SEF2 increased intracellular ROS production and cell susceptibility to CHG. This study revealed a novel mechanism by which CHG induced apoptosis of C. albicans cells through the disruption of metal ion and ROS homeostasis, which may help to identify new targets for fungal infections.
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Affiliation(s)
- Qian Jiang
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yuchen Deng
- Department of Dermatology, Second Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Shuaihu Li
- Department of Infectious Diseases, Huashan Hospital, Shanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Deqin Yang
- College of Stomatology, Chongqing Medical University, Chongqing, China
| | - Li Tao
- Department of Infectious Diseases, Huashan Hospital, Shanghai Institute of Infectious Disease and Biosecurity and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
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11
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Valtin J, Behrens S, Ruland A, Schmieder F, Sonntag F, Renner LD, Maitz MF, Werner C. A New In Vitro Blood Flow Model for the Realistic Evaluation of Antimicrobial Surfaces. Adv Healthc Mater 2023; 12:e2301300. [PMID: 37498721 DOI: 10.1002/adhm.202301300] [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: 04/24/2023] [Revised: 06/13/2023] [Indexed: 07/29/2023]
Abstract
Device-associated bloodstream infections can cause serious medical problems and cost-intensive postinfection management, defining a need for more effective antimicrobial coatings. Newly developed coatings often show reduced bacterial colonization and high hemocompatibility in established in vitro tests, but fail in animal studies or clinical trials. The poor predictive power of these models is attributed to inadequate representation of in vivo conditions. Herein, a new single-pass blood flow model, with simultaneous incubation of the test surface with bacteria and freshly-drawn human blood, is presented. The flow model is validated by comparative analysis of a recently developed set of antiadhesive and contact-killing polymer coatings, and the corresponding uncoated polycarbonate surfaces. The results confirm the model's ability to differentiate the antimicrobial activities of the studied surfaces. Blood activation data correlate with bacterial surface coverage: low bacterial adhesion is associated with low inflammation and hemostasis. Shear stress correlates inversely with bacterial colonization, especially on antiadhesive surfaces. The introduced model is concluded to enable the evaluation of novel antimicrobial materials under in vivo-like conditions, capturing interactions between bacteria and biomaterials surfaces in the presence of key components of the ex vivo host response.
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Affiliation(s)
- Juliane Valtin
- Leibniz Institute of Polymer Research Dresden, Institute of Biofunctional Polymer Materials, Hohe Strasse 6, 01069, Dresden, Germany
| | - Stephan Behrens
- Fraunhofer Institute for Material and Beam Technology IWS, 01277, Dresden, Germany
| | - André Ruland
- Leibniz Institute of Polymer Research Dresden, Institute of Biofunctional Polymer Materials, Hohe Strasse 6, 01069, Dresden, Germany
| | - Florian Schmieder
- Fraunhofer Institute for Material and Beam Technology IWS, 01277, Dresden, Germany
| | - Frank Sonntag
- Fraunhofer Institute for Material and Beam Technology IWS, 01277, Dresden, Germany
| | - Lars D Renner
- Leibniz Institute of Polymer Research Dresden, Institute of Biofunctional Polymer Materials, Hohe Strasse 6, 01069, Dresden, Germany
| | - Manfred F Maitz
- Leibniz Institute of Polymer Research Dresden, Institute of Biofunctional Polymer Materials, Hohe Strasse 6, 01069, Dresden, Germany
| | - Carsten Werner
- Leibniz Institute of Polymer Research Dresden, Institute of Biofunctional Polymer Materials, Hohe Strasse 6, 01069, Dresden, Germany
- Technische Universität Dresden, Cluster of Excellence Physics of Life, Center for Regenerative Therapies Dresden and Faculty of Chemistry and Food Chemistry, 01307, Dresden, Germany
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12
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Abutayyem H, Alam MK, Kanwal B, Alswairki HJ, Alogaibi YA. Sterilizing orthodontic appliances: A systematic review and meta-analysis on the available methods. J Orthod Sci 2023; 12:51. [PMID: 37881658 PMCID: PMC10597368 DOI: 10.4103/jos.jos_53_23] [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: 04/10/2023] [Revised: 04/27/2023] [Accepted: 04/27/2023] [Indexed: 10/27/2023] Open
Abstract
Infection control is essential to protect both the doctor and the patient by preventing the spread of infectious diseases. There is no exception in the field of dentistry, particularly in orthodontics, where numerous appliances are used for a variety of functions and also because the mouth cavity has the highest concentration of bacteria of any body part. Through this systematic review, we aimed to assess the various methods of sterilization employed in an orthodontic setting. Using relevant keywords, reference searches, and citation searches, the databases such as PubMed, MEDLINE, Web of Science, Cochrane, and Scopus were all searched; a total of 206 documents were found, of which 113 were initially selected. The remaining 23 distinct papers were initially made available after 90 publications that were identical to or similar to one another were eliminated. The final selection was made from eight documents that met all inclusion and exclusion requirements. The existing methods of sterilization were found to be competent in dealing with the microorganisms found in a typical orthodontic setting. The chemical method of sterilization was the norm in most of the studies that we assessed, with glutaraldehyde and peracetic acid (PAA) being the most commonly employed compounds for disinfection. PROSPERO Registration Number: CRD42022380831.
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Affiliation(s)
- Huda Abutayyem
- Department of Clinical Sciences, Center of Medical and Bio-Allied Health Sciences Research, College of Dentistry, Ajman University, Ajman, United Arab Emirates
| | - Mohammad Khursheed Alam
- Orthodontic Division, Preventive Dentistry Department, Orthodontic Division, College of Dentistry, Jouf University, Sakaka, Saudi Arabia
- Department of Dental Research Cell, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
- Department of Public Health, Faculty of Allied Health Sciences, Daffodil lnternational University, Ashulia, Dhaka, Bangladesh
| | - Bushra Kanwal
- Orthodontic Specialist, Practicing in Dental Clinic, AlBaha, Saudi Arabia
| | | | - Yahya A. Alogaibi
- Orthodontic Consultant, Aseer Specialized Dental Center, Abha, Saudi Arabia
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13
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Garrido L, Lyra P, Rodrigues J, Viana J, Mendes JJ, Barroso H. Revisiting Oral Antiseptics, Microorganism Targets and Effectiveness. J Pers Med 2023; 13:1332. [PMID: 37763100 PMCID: PMC10532628 DOI: 10.3390/jpm13091332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/24/2023] [Accepted: 08/27/2023] [Indexed: 09/29/2023] Open
Abstract
A good oral health status is mostly dependent on good oral hygiene habits, which knowingly impacts systemic health. Although controversial, chemical oral antiseptics can be useful in adjunct use to mechanical dental plaque control techniques in the prevention and management of local and overall health and well-being. This review aims to revisit, gather and update evidence-based clinical indications for the use of the most popular oral antiseptics, considering different types, microorganism targets and effectiveness in order to establish updated clinical recommendations.
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Affiliation(s)
| | | | | | | | | | - Helena Barroso
- Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Caparica, 2829-511 Almada, Portugal (P.L.); (J.V.); (J.J.M.)
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14
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Monstrey SJ, Govaers K, Lejuste P, Lepelletier D, Ribeiro de Oliveira P. Evaluation of the role of povidone‑iodine in the prevention of surgical site infections. Surg Open Sci 2023; 13:9-17. [PMID: 37034245 PMCID: PMC10074992 DOI: 10.1016/j.sopen.2023.03.005] [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: 12/19/2022] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/18/2023] Open
Abstract
Background The occurrence of surgical site infections (SSIs) is associated with increased risk of mortality, development of other infections, and the need for reintervention, posing a significant health burden. The aim of this review was to examine the current data and guidelines around the use of antiseptic povidone‑iodine (PVP-I) for the prevention of SSIs at each stage of surgical intervention. Methods A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertise. Results Scientific evidence demonstrates that PVP-I can be used at every stage of surgical intervention: preoperative, intraoperative, and postoperative. PVP-I is one of the most widely used antiseptics on healthy skin and mucous membranes for preoperative surgical site preparation and is associated with a low SSI rate. For intraoperative irrigation, aqueous PVP-I is the recommended agent and has been demonstrated to decrease SSIs in a range of surgical settings, and for postoperative wound healing, there is a growing body of evidence to support the use of PVP-I. Conclusions There is a need for more stringent study designs in clinical trials to enable meaningful comparisons between antiseptic agents, particularly for preoperative skin preparation. The use of a single agent (PVP-I) at each stage of surgical intervention could potentially provide advantages, including economic benefits, over agents that can only be used at discrete stages of the surgical procedure. Key message Evidence supports the use of PVP-I at all stages of surgical intervention, from preoperative measures (including skin preparation, preoperative washing, and nasal decolonization) to intraoperative irrigation, through to postoperative wound management. However, there is a need for more stringent study designs in clinical trials to enable meaningful comparisons between antiseptic agents, particularly for preoperative skin preparation.
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Affiliation(s)
- Stan J. Monstrey
- Burn Care Center, Plastic Surgery Department, University Hospital Ghent, Ghent, Belgium
| | - Kris Govaers
- Division of Orthopaedic Surgery, az Sint-Blasius, Dendermonde, Belgium
| | - Patrice Lejuste
- Department of Oral and Maxillofacial Surgery, Grand Hôpital de Charleroi, Charleroi, Belgium
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15
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Bencze B, Temesfői V, Das S, Papp H, Kaltenecker P, Kuczmog A, Jakab F, Kocsis B, Kőszegi T. Development of a novel, entirely herbal-based mouthwash effective against common oral bacteria and SARS-CoV-2. BMC Complement Med Ther 2023; 23:138. [PMID: 37127611 PMCID: PMC10150350 DOI: 10.1186/s12906-023-03956-3] [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: 07/28/2022] [Accepted: 04/11/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND Parallel to the growth of the oral healthcare market, there is a constantly increasing demand for natural products as well. Many customers prefer products that contain fewer toxic agents, therefore providing an environmentally friendly solution with the benefit of smaller risk to the user. Medieval and early modern medicinal knowledge might be useful when looking for natural, herbal-based components to develop modern products. Along with these considerations we created, tested, and compared an entirely natural mouthwash, named Herba Dei. METHODS The manufacturing procedure was standardized, and the created tincture was evaluated by GC/MS analysis for active compounds, experimentally tested in cell-based cytotoxicity, salivary protein integrity, cell-free antioxidant activity, anti-bacterial and anti-viral assays, and compared with three market-leading mouthwashes. RESULTS Our tincture did not show significant damage in the cytotoxicity assays to keratinocyte and Vero E6 cells and did not disrupt the low molecular weight salivary proteins. Its radical scavenging capacity surpassed that of two tested, partly natural, and synthetic mouthwashes, while its antibacterial activity was comparable to the tested products, or higher in the bacterial aerobic respiratory assay. The active compounds responsible for the effects include naturally occurring phenylpropanoids, terpenes, and terpenoids. Our mouthwash proved to be effective in vitro in lowering the copy number of SARS-CoV-2 in circumstances mimicking the salivary environment. CONCLUSIONS The developed product might be a useful tool to impede the transmission and spread of SARS-CoV-2 in interpersonal contact and aerosol-generating conditions. Our mouthwash can help reduce the oral bacterial flora and has an antioxidant activity that facilitates wound healing and prevents adverse effects of smoke in the oral cavity.
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Affiliation(s)
- Bálint Bencze
- Department of Laboratory Medicine, Clinical Centre, Medical School, University of Pécs, Ifjúság Út 13, Pécs, 7624, Hungary
| | - Viktória Temesfői
- Department of Laboratory Medicine, Clinical Centre, Medical School, University of Pécs, Ifjúság Út 13, Pécs, 7624, Hungary.
- Lab-On-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary.
- Hungarian National Laboratory On Reproduction, University of Pécs, Pécs, 7624, Hungary.
| | - Sourav Das
- Department of Laboratory Medicine, Clinical Centre, Medical School, University of Pécs, Ifjúság Út 13, Pécs, 7624, Hungary
- Lab-On-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
| | - Henrietta Papp
- National Laboratory of Virology, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
- Institute of Biology, Faculty of Sciences, University of Pécs, Ifjúság Útja 6, Pécs, 7624, Hungary
| | - Péter Kaltenecker
- Lab-On-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
- Hungarian National Laboratory On Reproduction, University of Pécs, Pécs, 7624, Hungary
| | - Anett Kuczmog
- National Laboratory of Virology, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
- Institute of Biology, Faculty of Sciences, University of Pécs, Ifjúság Útja 6, Pécs, 7624, Hungary
| | - Ferenc Jakab
- National Laboratory of Virology, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
- Institute of Biology, Faculty of Sciences, University of Pécs, Ifjúság Útja 6, Pécs, 7624, Hungary
| | - Béla Kocsis
- Department of Medical Microbiology and Immunology, Clinical Centre, Medical School, University of Pécs, Szigeti Út 12, Pécs, 7624, Hungary
| | - Tamás Kőszegi
- Department of Laboratory Medicine, Clinical Centre, Medical School, University of Pécs, Ifjúság Út 13, Pécs, 7624, Hungary
- Lab-On-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság Útja 20, Pécs, 7624, Hungary
- Hungarian National Laboratory On Reproduction, University of Pécs, Pécs, 7624, Hungary
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16
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Abbood HM, Hijazi K, Gould IM. Chlorhexidine Resistance or Cross-Resistance, That Is the Question. Antibiotics (Basel) 2023; 12:antibiotics12050798. [PMID: 37237701 DOI: 10.3390/antibiotics12050798] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/03/2023] [Accepted: 04/17/2023] [Indexed: 05/28/2023] Open
Abstract
Chlorohexidine (CHX) is a widely used biocide in clinical and household settings. Studies over the last few decades have reported CHX resistance in different bacterial species, but at concentrations well below those used in the clinical setting. Synthesis of these findings is hampered by the inconsistent compliance with standard laboratory procedures for biocide susceptibility testing. Meanwhile, studies of in vitro CHX-adapted bacteria have reported cross-resistance between CHX and other antimicrobials. This could be related to common resistance mechanisms of CHX and other antimicrobials and/or the selective pressure driven by the intensive use of CHX. Importantly, CHX resistance and cross-resistance to antimicrobials should be investigated in clinical as well as environmental isolates to further our understanding of the role of CHX in selection of multidrug resistance. Whilst clinical studies to support the hypothesis of CHX cross-resistance with antibiotics are currently lacking, we recommend raising the awareness of healthcare providers in a range of clinical disciplines regarding the potential adverse impact of the unfettered use of CHX on tackling antimicrobial resistance.
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Affiliation(s)
- Hadeel Mohammed Abbood
- Institute of Dentistry, School of Medicine, Medical Science and Nutrition, University of Aberdeen, Aberdeen AB25 2ZR, UK
- College of Dentistry, Tikrit University, Tikrit 34001, Iraq
| | - Karolin Hijazi
- Institute of Dentistry, School of Medicine, Medical Science and Nutrition, University of Aberdeen, Aberdeen AB25 2ZR, UK
| | - Ian M Gould
- Department of Medical Microbiology, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK
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17
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Oliveira RWG, de Oliveira JM, da Paz FB, Muniz EC, de Moura EM, Costa JCS, do Nascimento MO, Carvalho ALM, Pinheiro IM, Mendes AN, Filgueiras LA, de Souza PR, de Moura CVR. Films composed of white angico gum and chitosan containing chlorhexidine as an antimicrobial agent. Int J Biol Macromol 2023; 235:123905. [PMID: 36870650 DOI: 10.1016/j.ijbiomac.2023.123905] [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: 07/29/2022] [Revised: 02/12/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023]
Abstract
Anadenanthera colubrina, popularly known as white angico, is a species extensively cultivated in Brazil, mainly in the cerrado region, including the state of Piauí. This study examines the development of films composed of white angico gum (WAG) and chitosan (CHI) and containing chlorhexidine (CHX), an antimicrobial agent. The solvent casting method was used to prepare films. Different combinations and concentrations of WAG and CHI were used to obtain films with good physicochemical characteristics. Properties such as the in vitro swelling ratio, the disintegration time, folding endurance, and the drug content were determined. The selected formulations were characterised by scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction, and the CHX release time and antimicrobial activity were evaluated. CHX showed a homogenous distribution in all CHI/WAG film formulations. The optimised films showed good physicochemical properties with 80% CHX release over 26 h, which is considered promising for local treatment of severe lesions in the mouth. Cytotoxicity tests of the films did not show toxicity. The antimicrobial and antifungal effects were very effective against the tested microorganisms.
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Affiliation(s)
| | | | | | - Edvani Curti Muniz
- Department of Chemistry, Federal University of Piauí, 64049-550, Brazil.
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18
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Liu T, Chen YC, Jeng SL, Chang JJ, Wang JY, Lin CH, Tsai PF, Ko NY, Ko WC, Wang JL. Short-term effects of Chlorhexidine mouthwash and Listerine on oral microbiome in hospitalized patients. Front Cell Infect Microbiol 2023; 13:1056534. [PMID: 36816590 PMCID: PMC9932516 DOI: 10.3389/fcimb.2023.1056534] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 01/20/2023] [Indexed: 02/05/2023] Open
Abstract
Introduction Chlorhexidine (CHX) and essential oil containing mouthwashes like Listerine® can improve oral hygiene via suppressing oral microbes. In hospitalized patients, CHX mouthwash reduces the incidence of ventilator-associated pneumonia. However, CHX use was also associated with increased mortality, which might be related to nitrate-reducing bacteria. Currently, no study determines oral bacteria targeted by essential oils mouthwash in hospitalized patients using a metagenomic approach. Methods We recruited 87 hospitalized patients from a previous randomized control study, and assigned them to three mouthwash groups: CHX, Listerine, and normal saline (control). Before and after gargling the mouthwash twice a day for 5-7 days, oral bacteria were examined using a 16S rDNA approach. Results Alpha diversities at the genus level decreased significantly only for the CHX and Listerine groups. Only for the two groups, oral microbiota before and after gargling were significantly different, but not clearly distinct. Paired analysis eliminated the substantial individual differences and revealed eight bacterial genera (including Prevotella, Fusobacterium, and Selenomonas) with a decreased relative abundance, while Rothia increased after gargling the CHX mouthwash. After gargling Listerine, seven genera (including Parvimonas, Eubacterium, and Selenomonas) showed a decreased relative abundance, and the magnitudes were smaller compared to the CHX group. Fewer bacteria targeted by Listerine were reported to be nitrate-reducing compared to the CHX mouthwash. Discussion In conclusion, short-term gargling of the CHX mouthwash and Listerine altered oral microbiota in our hospitalized patients. The bacterial genera targeted by the CHX mouthwash and Listerine were largely different and the magnitudes of changes were smaller using Listerine. Functional alterations of gargling CHX and Listerine were also different. These findings can be considered for managing oral hygiene of hospitalized patients.
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Affiliation(s)
- Tsunglin Liu
- Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Chin Chen
- Department of Nursing, National Cheng Kung University Hospital, Tainan, Taiwan,Department of Nursing, National Cheng Kung University, Tainan, Taiwan
| | - Shuen-Lin Jeng
- Department of Statistics, Institute of Data Science, Center for Innovative FinTech Business Models, National Cheng Kung University, Tainan, Taiwan
| | - Jui-Jen Chang
- Graduate Institute of Integrated Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Jiu-Yao Wang
- Center of Allergy, Immunology and Microbiome (AIM), Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan
| | - Cheng-Han Lin
- Center of Allergy, Immunology and Microbiome (AIM), Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan
| | - Pei-Fang Tsai
- Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Nai-Ying Ko
- Department of Nursing, National Cheng Kung University Hospital, Tainan, Taiwan,Department of Nursing, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan,Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jiun-Ling Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan,Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan,*Correspondence: Jiun-Ling Wang,
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19
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An open-source computational tool for measuring bacterial biofilm morphology and growth kinetics upon one-sided exposure to an antimicrobial source. Sci Rep 2022; 12:16125. [PMID: 36167741 PMCID: PMC9515175 DOI: 10.1038/s41598-022-20275-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 09/12/2022] [Indexed: 11/28/2022] Open
Abstract
Bacillus subtilis biofilms are well known for their complex and highly adaptive morphology. Indeed, their phenotypical diversity and intra-biofilm heterogeneity make this gram-positive bacterium the subject of many scientific papers on the structure of biofilms. The “robustness” of biofilms is a term often used to describe their level of susceptibility to antimicrobial agents and various mechanical and molecular inhibition/eradication methods. In this paper, we use computational analytics to quantify Bacillus subtilis morphological response to proximity to an antimicrobial source, in the form of the antiseptic chlorhexidine. Chlorhexidine droplets, placed in proximity to Bacillus subtilis macrocolonies at different distances result in morphological changes, quantified using Python-based code, which we have made publicly available. Our results quantify peripheral and inner core deformation as well as differences in cellular viability of the two regions. The results reveal that the inner core, which is often characterized by the presence of wrinkled formations in the macrocolony, is more preserved than the periphery. Furthermore, the paper describes a crescent-shaped colony morphology which occurs when the distance from the chlorhexidine source is 0.5 cm, as well as changes observed in the growth substrate of macrocolonies exposed to chlorhexidine.
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Pattananandecha T, Sirilun S, Apichai S, Ouirungroj T, Uirungroj P, Ogata F, Kawasaki N, Saenjum C. Pharmaceutical Incompatibility of Lubricating Gel Formulation Reduces Antibacterial Activity of Chlorhexidine Gluconate: In Vitro Study in Northern Thailand. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:12285. [PMID: 36231587 PMCID: PMC9566729 DOI: 10.3390/ijerph191912285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/21/2022] [Accepted: 09/22/2022] [Indexed: 06/16/2023]
Abstract
Chlorhexidine gluconate (CHG) is a cationic disinfectant. The positive charge of CHG molecules binds to phospholipid's negative charge in bacterial cell walls, causing membrane disruption. The in vitro kinetic physical, chemical and biological incompatibilities of nine lubricating gels with 1% w/v CHG were investigated. Five containing anionic thickener, two containing nonionic thickener, and two containing cationic thickener were collected from hospitals in northern Thailand. All the anionic and nonionic lubricating gels significantly reduced (p < 0.05) the CHG amount after 5 min of exposure time from 12.54% to 54.99%, respectively. In contrast, the amount of CHG exposed with cationic lubricating gels was maintained. Antibacterial activity was significantly reduced to a 1.17-4.33 log10 reduction for Staphylococcus aureus ATCC25923 and a 1.07-3.52 log10 reduction for Escherichia coli ATCC25922 after 5 min exposure to all anionic and nonionic lubricating gels. In contrast, the two cationic lubricating gels maintained the antibacterial activity of the CHG solution (5.69 ± 0.14 and 5.45 ± 0.17 log10 reduction). The results suggest that anionic and nonionic thickeners in lubricating gel formulations may neutralize the positive charge and reduce the antibacterial activity of CHG, reducing its effectiveness as a disinfectant.
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Affiliation(s)
- Thanawat Pattananandecha
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Sasithorn Sirilun
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Sutasinee Apichai
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Teerapat Ouirungroj
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Pose Health Care Co., Ltd., 1 Soi Ramintra 107, Ramintra Rd., Kannayao, Bangkok 10230, Thailand
| | - Phisit Uirungroj
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Pose Health Care Co., Ltd., 1 Soi Ramintra 107, Ramintra Rd., Kannayao, Bangkok 10230, Thailand
| | - Fumihiko Ogata
- Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan
| | - Naohito Kawasaki
- Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan
- Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan
| | - Chalermpong Saenjum
- Center of Excellence for Innovation in Analytical Science and Technology for Biodiversity-Based Economic and Society (I-ANALY-S-T_B.BES-CMU), Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
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21
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Mármol I, Quero J, Azcárate P, Atrián-Blasco E, Ramos C, Santos J, Gimeno MC, Rodríguez-Yoldi MJ, Cerrada E. Biological Activity of NHC-Gold-Alkynyl Complexes Derived from 3-Hydroxyflavones. Pharmaceutics 2022; 14:pharmaceutics14102064. [PMID: 36297498 PMCID: PMC9612383 DOI: 10.3390/pharmaceutics14102064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/19/2022] [Accepted: 09/23/2022] [Indexed: 11/17/2022] Open
Abstract
In this paper we describe the synthesis of new N-heterocyclic carbene (NHC) gold(I) derivatives with flavone-derived ligands with a propargyl ether group. The compounds were screened for their antimicrobial and anticancer activities, showing greater activity against bacteria than against colon cancer cells (Caco-2). Complexes [Au(L2b)(IMe)] (1b) and [Au(L2b)(IPr)] (2b) were found to be active against both Gram-positive and Gram-negative strains. The mechanism of action of 1b was evaluated by measurement of thioredoxin reductase (TrxR) and dihydrofolate reductase (DHFR) activity, besides scanning electron microscopy (SEM). Inhibition of the enzyme thioredoxin reductase is not observed in either Escherichia Coli or Caco-2 cells; however, DHFR activity is compromised after incubation of E. coli cells with complex 1b. Moreover, loss of structural integrity and change in bacterial shape is observed in the images obtained from scanning electron microscopy (SEM) after treatment E. coli cells with complex 1b.
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Affiliation(s)
- Inés Mármol
- Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Departamento de Farmacología y Fisiología, Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, CIBERobn, IIS Aragón, IA2, 50013 Zaragoza, Spain
| | - Javier Quero
- Departamento de Farmacología y Fisiología, Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, CIBERobn, IIS Aragón, IA2, 50013 Zaragoza, Spain
| | - Paula Azcárate
- Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Elena Atrián-Blasco
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain
| | - Carla Ramos
- Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Viana do Castelo, Avenida do Atlântico No. 644, 4900-348 Viana do Castelo, Portugal
| | - Joana Santos
- Escola Superior de Tecnologia e Gestão, Instituto Politécnico de Viana do Castelo, Avenida do Atlântico No. 644, 4900-348 Viana do Castelo, Portugal
| | - María Concepción Gimeno
- Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - María Jesús Rodríguez-Yoldi
- Departamento de Farmacología y Fisiología, Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, CIBERobn, IIS Aragón, IA2, 50013 Zaragoza, Spain
- Correspondence: (M.J.R.-Y.); (E.C.)
| | - Elena Cerrada
- Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., Pedro Cerbuna 12, 50009 Zaragoza, Spain
- Correspondence: (M.J.R.-Y.); (E.C.)
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22
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Haerussana ANEM, Ayuhastuti A, Yuniar SF, Bustami HA, Widyastiwi W. Taro (Colosia esculenta) Leaves Extract Inhibits Streptococcus mutans ATCC 31987. BORNEO JOURNAL OF PHARMACY 2022. [DOI: 10.33084/bjop.v5i3.3156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Dental caries was the most common disease in both adults and children. Streptococcus mutans is the main bacteria causing plaque formation and was the initiator of dental caries. Antibacterials derived from plants can be used to prevent plaque formation. Taro (Colosia esculenta) has been used in traditional medicine. Antibacterial compounds have been discovered in C. esculenta leaves. This study aimed to determine the ability of C. esculenta leaf ethanol extract to inhibit the growth of S. mutans ATCC 31987. Simplicia preparation, extract preparation, and phytochemical screening was carried out. Then, the antibacterial activity test was performed using the disc diffusion method to determine the zone of inhibition at various concentrations of 10, 20, 30, 40, 50, 60, and 70%. Colosia esculenta leaf ethanol extract contains alkaloids, flavonoids, triterpenoids, saponins, and produces an inhibition zone at each concentration variation. Very strong antibacterial activity was produced at a concentration of 70% at 21.11±0.46 mm, which was higher than the positive control.
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23
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Singkham-In U, Phuengmaung P, Makjaroen J, Saisorn W, Bhunyakarnjanarat T, Chatsuwan T, Chirathaworn C, Chancharoenthana W, Leelahavanichkul A. Chlorhexidine Promotes Psl Expression in Pseudomonas aeruginosa That Enhances Cell Aggregation with Preserved Pathogenicity Demonstrates an Adaptation against Antiseptic. Int J Mol Sci 2022; 23:ijms23158308. [PMID: 35955437 PMCID: PMC9368580 DOI: 10.3390/ijms23158308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/20/2022] [Accepted: 07/25/2022] [Indexed: 11/16/2022] Open
Abstract
Because Pseudomonas aeruginosa is frequently in contact with Chlorhexidine (a regular antiseptic), bacterial adaptations are possible. In comparison with the parent strain, the Chlorhexidine-adapted strain formed smaller colonies with metabolic downregulation (proteomic analysis) with the cross-resistance against colistin (an antibiotic for several antibiotic-resistant bacteria), partly through the modification of L-Ara4N in the lipopolysaccharide at the outer membrane. Chlorhexidine-adapted strain formed dense liquid–solid interface biofilms with enhanced cell aggregation partly due to the Chlorhexidine-induced overexpression of psl (exopolysaccharide-encoded gene) through the LadS/GacSA pathway (c-di-GMP-independence) in 12 h biofilms and maintained the aggregation with SiaD-mediated c-di-GMP dependence in 24 h biofilms as evaluated by polymerase chain reaction (PCR). The addition of Ca2+ in the Chlorhexidine-adapted strain facilitated several Psl-associated genes, indicating an impact of Ca2+ in Psl production. The activation by Chlorhexidine-treated sessile bacteria demonstrated a lower expression of IL-6 and IL-8 on fibroblasts and macrophages than the activation by the parent strain, indicating the less inflammatory reactions from Chlorhexidine-exposed bacteria. However, the 14-day severity of the wounds in mouse caused by Chlorhexidine-treated bacteria versus the parent strain was similar, as indicated by wound diameters and bacterial burdens. In conclusion, Chlorhexidine induced psl over-expression and colistin cross-resistance that might be clinically important.
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Affiliation(s)
- Uthaibhorn Singkham-In
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (U.S.-I.); (P.P.); (C.C.)
| | - Pornpimol Phuengmaung
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (U.S.-I.); (P.P.); (C.C.)
| | - Jiradej Makjaroen
- Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand;
| | - Wilasinee Saisorn
- Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (W.S.); (T.B.)
| | - Thansita Bhunyakarnjanarat
- Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (W.S.); (T.B.)
| | - Tanittha Chatsuwan
- Antimicrobial Resistance and Stewardship Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand;
| | - Chintana Chirathaworn
- Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (U.S.-I.); (P.P.); (C.C.)
| | - Wiwat Chancharoenthana
- Tropical Nephrology Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Correspondence: (W.C.); (A.L.); Tel.: +66-2-306-9130 (W.C.); +66-2-256-4251 (A.L.); Fax: +66-2-354-9150 (W.C.); +66-2-252-6920 (A.L.)
| | - Asada Leelahavanichkul
- Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, 1873 Rama 4 Road, Pathumwan, Bangkok 10330, Thailand; (W.S.); (T.B.)
- Correspondence: (W.C.); (A.L.); Tel.: +66-2-306-9130 (W.C.); +66-2-256-4251 (A.L.); Fax: +66-2-354-9150 (W.C.); +66-2-252-6920 (A.L.)
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24
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Gregorchuk BSJ, Reimer SL, Slipski CJ, Milner KA, Hiebert SL, Beniac DR, Booth TF, Zhanel GG, Bay DC. Applying fluorescent dye assays to discriminate Escherichia coli chlorhexidine resistance phenotypes from porin and mlaA deletions and efflux pumps. Sci Rep 2022; 12:12149. [PMID: 35840757 PMCID: PMC9287405 DOI: 10.1038/s41598-022-15775-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/29/2022] [Indexed: 11/21/2022] Open
Abstract
Bacterial resistance to the antiseptic chlorhexidine (CHX), is a growing problem, recently shown to be caused by deleterious mutations to the phospholipid transport system component (mlaA) as well as efflux pump overexpression. Comparisons of CHX resistance mechanisms, such as porin deletions (ompCF), and over-expressed efflux pumps (acrB, qacE, aceI), are lacking and may be distinguishable using antiseptic rapid fluorescent dye testing assays. Using E. coli K-12 CHX adapted isolates (CHXR1), gene deletion mutants, and over-expressed transformants the phenotypes of these CHX resistance genes were compared using antimicrobial susceptibility tests (AST), rapid fluorescent propidium iodide dye-based membrane integrity assays (RFDMIA), and scanning electron microscopy (SEM). AST findings showed CHXR1, ΔacrB, ΔompCF, and transformants pCA24N-aceI and pCA24N-mlaA conferred greater (two to fourfold) MIC changes when compared to matched controls. Examination of these mutants/transformants using CHX RFDMIA showed that porin dual-deletions (ΔompCF) and mlaA alterations (ΔmlaA; pCA24N-mlaA, CHXR1) were distinguishable from controls. Results for over-expressed (pMS119EH-aceI) and deleted (ΔacrB) efflux pump RFDMIA could not be distinguished with propidium iodide, only with ethidium bromide, suggesting propidium iodide is better suited for detecting porin and mlaA associated CHX resistance mechanisms. SEM of CHXR1 and unadapted E. coli cells exposed to increasing CHX concentrations revealed that CHX does not visibly damage cell envelope integrity at any tested concentration but did identify elongated CHXR1 cells. ΔmlaA confers similar levels of CHX resistance as efflux overexpression and porin deletions, however, only outer membrane-altering porin and mlaA deletions can be reliably distinguished using RFDMIA.
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Affiliation(s)
- Branden S J Gregorchuk
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Shelby L Reimer
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Carmine J Slipski
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Kieran A Milner
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Shannon L Hiebert
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Daniel R Beniac
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Timothy F Booth
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Denice C Bay
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Rm 514C Basic Medical Sciences Bldg, 745 Bannatyne Avenue, Winnipeg, MB, R3E 0J9, Canada.
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25
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Is Lipid Specificity Key to the Potential Antiviral Activity of Mouthwash Reagent Chlorhexidine against SARS-CoV-2? MEMBRANES 2022; 12:membranes12060616. [PMID: 35736323 PMCID: PMC9230368 DOI: 10.3390/membranes12060616] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/31/2022] [Accepted: 06/07/2022] [Indexed: 11/17/2022]
Abstract
Chlorhexidine (CHX), a popular antibacterial drug, is widely used for oral health. Emerging pieces of evidence suggest that commercially available chlorhexidine mouthwash formulations are effective in suppressing the spread of SARS-CoV-2, possibly through destabilization of the viral lipid envelope. CHX is known for its membrane-active properties; however, the molecular mechanism revealing how it damages the viral lipid envelope is yet to be understood. Here we used extensive conventional and umbrella sampling simulations to quantify the effects of CHX on model membranes mimicking the composition of the SARS-CoV-2 outer lipid membrane as well as the host plasma membrane. Our results show that the lipid composition and physical properties of the membrane play an important role in binding and insertion, with CHX binding favorably to the viral membrane over the plasma membrane. Among the simulated lipids, CHX preferentially binds to anionic lipids, PS and PI, which are more concentrated in the viral membrane. The deeper and stable binding of CHX to the viral membrane results in more pronounced swelling of the membrane laterally with a thinning of the bilayer. The overall free energies of pore formation are strongly reduced for the viral membrane compared to the plasma membrane; however, CHX has a larger concentration-dependent effect on free energies of pore formation in the plasma membrane than the viral membrane. The results indicate that CHX is less toxic to the human plasma membrane at low concentrations. Our simulations reveal that CHX facilitates pore formation by the combination of thinning the membrane and accumulation at the water defect. This study provides insights into the mechanism underlying the anti-SARS-CoV-2 potency of CHX, supporting its potential for application as an effective and safe oral rinse agent for preventing viral transmission.
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Chug MK, Massoumi H, Wu Y, Brisbois E. Prevention of medical device infections via multi-action nitric oxide and chlorhexidine diacetate releasing medical grade silicone biointerfaces. J Biomed Mater Res A 2022; 110:1263-1277. [PMID: 35170212 PMCID: PMC8986591 DOI: 10.1002/jbm.a.37372] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 01/21/2022] [Accepted: 02/01/2022] [Indexed: 12/25/2022]
Abstract
The presence of bacteria and biofilm on medical device surfaces has been linked to serious infections, increased health care costs, and failure of medical devices. Therefore, antimicrobial biointerfaces and medical devices that can thwart microbial attachment and biofilm formation are urgently needed. Both nitric oxide (NO) and chlorhexidine diacetate (CHXD) possess broad-spectrum antibacterial properties. In the past, individual polymer release systems of CHXD and NO donor S-nitroso-N-acetylpenicillamine (SNAP) incorporated polymer platforms have attracted considerable attention for biomedical/therapeutic applications. However, the combination of the two surfaces has not yet been explored. Herein, the synergy of NO and CHXD was evaluated to create an antimicrobial medical-grade silicone rubber. The 10 wt% SNAP films were fabricated using solvent casting with a topcoat of CHXD (1, 3, and 5 wt%) to generate a dual-active antibacterial interface. Chemiluminescence studies confirmed the NO release from SNAP-CHXD films at physiologically relevant levels (0.5-4 × 10-10 mol min-1 cm-2 ) for at least 3 weeks and CHXD release for at least 7 days. Further characterization of the films via SEM-EDS confirmed uniform distribution of SNAP and presence of CHXD within the polymer films without substantial morphological changes, as confirmed by contact angle hysteresis. Moreover, the dual-active SNAP-CHXD films were able to significantly reduce Escherichia coli and Staphylococcus aureus bacteria (>3-log reduction) compared to controls with no explicit toxicity towards mouse fibroblast cells. The synergy between the two potent antimicrobial agents will help combat bacterial contamination on biointerfaces and enhance the longevity of medical devices.
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Affiliation(s)
- Manjyot Kaur Chug
- School of Chemical, Materials & Biomedical Engineering, University of Georgia, Athens, GA USA
| | - Hamed Massoumi
- School of Chemical, Materials & Biomedical Engineering, University of Georgia, Athens, GA USA
| | - Yi Wu
- School of Chemical, Materials & Biomedical Engineering, University of Georgia, Athens, GA USA
| | - Elizabeth Brisbois
- School of Chemical, Materials & Biomedical Engineering, University of Georgia, Athens, GA USA
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27
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van de Lagemaat M, Stockbroekx V, Geertsema-Doornbusch GI, Dijk M, Carniello V, Woudstra W, van der Mei HC, Busscher HJ, Ren Y. A Comparison of the Adaptive Response of Staphylococcus aureus vs. Streptococcus mutans and the Development of Chlorhexidine Resistance. Front Microbiol 2022; 13:861890. [PMID: 35694293 PMCID: PMC9186159 DOI: 10.3389/fmicb.2022.861890] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 04/11/2022] [Indexed: 11/14/2022] Open
Abstract
Antimicrobials with nonselective antibacterial efficacy such as chlorhexidine can be effective in reducing biofilm, but bear the risk of inducing resistance in specific bacteria. In clinical practice, bacteria such as Staphylococcus aureus have been found resistant to chlorhexidine, but other bacteria, including Streptococcus mutans, have largely remained susceptible to chlorhexidine despite its widespread use in oral healthcare. Here, we aim to forward a possible reason as to why S. aureus can acquire resistance against chlorhexidine, while S. mutans remains susceptible to chlorhexidine. Measurement of surface-enhanced fluorescence indicated that chlorhexidine caused gradual, but irreversible deformation to adhering green fluorescent S. aureus due to irreparable damage to the cell wall. Concurrently, the metabolic activity of adhering staphylococci was higher than of planktonic bacteria, suggesting efflux mechanisms may have been activated upon cell wall deformation, impeding the buildup of a high chlorhexidine concentration in the cytoplasm and therewith stimulating the development of chlorhexidine resistance in S. aureus. Exposure of S. mutans to chlorhexidine caused immediate, but reversible deformation in adhering streptococci, indicative of rapid self-repair of cell wall damage done by chlorhexidine. Due to cell wall self-repair, S. mutans will be unable to effectively reduce the chlorhexidine concentration in the cytoplasm causing solidification of the cytoplasm. In line, no increased metabolic activity was observed in S. mutans during exposure to chlorhexidine. Therewith, self-repair is suicidal and prevents the development of a chlorhexidine-resistant progeny in S. mutans.
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Affiliation(s)
- Marieke van de Lagemaat
- University of Groningen and University Medical Center Groningen, Department of Orthodontics, Groningen, Netherlands
| | - Valerie Stockbroekx
- University of Groningen and University Medical Center Groningen, Department of Orthodontics, Groningen, Netherlands
| | - Gésinda I. Geertsema-Doornbusch
- University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands
| | - Melissa Dijk
- University of Groningen and University Medical Center Groningen, Department of Orthodontics, Groningen, Netherlands
| | - Vera Carniello
- University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands
| | - Willem Woudstra
- University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands
| | - Henny C. van der Mei
- University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands
- *Correspondence: Henny C. van der Mei,
| | - Henk J. Busscher
- University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Groningen, Netherlands
| | - Yijin Ren
- University of Groningen and University Medical Center Groningen, Department of Orthodontics, Groningen, Netherlands
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28
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AlHelal AA. Disinfection efficacy and fracture strength of PMMA denture-based polymer with chlorhexidine, PDT utilizing Rose Bengal and hematoporphyrin, and Er, Cr: YSGG laser. Photodiagnosis Photodyn Ther 2022; 37:102640. [PMID: 34823033 DOI: 10.1016/j.pdpdt.2021.102640] [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: 11/07/2021] [Revised: 11/15/2021] [Accepted: 11/19/2021] [Indexed: 11/20/2022]
Abstract
OBJECTIVE The study aimed to assess and compare disinfection efficacy and fracture strength of PMMA based DBPs using chlorhexidine (CHX), PDT utilizing Rose Bengal (RB) and hematoporphyrin HPD, and Er,Cr:YSGG laser (ECL) induced antimicrobial action against in-vitro biofilms colonized with C.albicans, S.aureus, S. mutans, and E. coli. MATERIAL AND METHODS American Type Culture Collection (ATCC) of C.albicans, S.aureus, S. mutans and E. coli were cultured. Forty-eight PMMA-based denture base plates (DBPs) were prepared by heat-cure acrylic resin and contaminated by in-vitro biofilm under-stimulated in-vitro conditions. DBPs were treated with group1; ECL group 2; RB 5µm, group 3; HPD 500 mg/L and group 4; 0.12% CHX (controls) respectively, for the disinfection of biofilms. All photosensitizers (PS) were activated by LED at a different wavelength. Each contaminated DBP was sprayed on all its surfaces with the aforementioned photosensitizers and CHX. One-way analysis of variance (ANOVA) was used to test the efficacy of disinfection and fracture load testing. Tukey multiple comparison tests were performed to compare means of CFU/mL (log10) for exposed E. coli, C. albicans, S aureus, and S. mutans. RESULTS Specimens in group 1 disinfected with erbium laser, group 3 disinfected with HPD, and group 4 sterilized with chemical disinfection were effective in decreasing bacterial load CFU/mL (log10) against C.albicans, S. aureus, S.mutans, and E. Coli (p>0.05). Intergroup comparison demonstrated ECL, CHX and HPD demonstrated a comparable reduction against C.albicans and S.aureus (p>0.05). Similarly, S.mutans and E.coli were sensitive against all experimental groups (p>0.05). no significant difference in fractural load analysis among the different investigated groups was noted (p>0.05). CONCLUSION ECL and HPD photosensitizer revealed a significant reduction in CFU/ml of exposed viable colonies of C.albicans, S.aureus, S. mutans, and E. coli comparable to 0.12% CHX mediated disinfection of PMMA-based DBPs. Irrespective of the type of disinfection no influence of disinfection was noted on the fracture load of PMMA DBPs.
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Affiliation(s)
- Abdulaziz A AlHelal
- Department Of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.
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Carbon nanogels exert multipronged attack on resistant bacteria and strongly constrain resistance evolution. J Colloid Interface Sci 2022; 608:1813-1826. [PMID: 34742090 DOI: 10.1016/j.jcis.2021.10.107] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 10/16/2021] [Accepted: 10/18/2021] [Indexed: 12/19/2022]
Abstract
Developing antimicrobial agents that can eradicate drug-resistant (DR) bacteria and provide sustained protection from DR bacteria is a major challenge. Herein, we report a mild pyrolysis approach to prepare carbon nanogels (CNGs) through polymerization and the partial carbonization of l-lysine hydrochloride at 270 °C as a potential broad-spectrum antimicrobial agent that can inhibit biopolymer-producing bacteria and clinical drug-resistant isolates and tackle drug resistance issues. We thoroughly studied the structures of the CNGs, their antibacterial mechanism, and biocompatibility. CNGs possess superior bacteriostatic effects against drug-resistant bacteria compared to some commonly explored antibacterial nanomaterials (silver, copper oxide, and zinc oxide nanoparticles, and graphene oxide) through multiple antimicrobial mechanisms, including reactive oxygen species generation, membrane potential dissipation, and membrane function disruption, due to the positive charge and flexible colloidal structures resulting strong interaction with bacterial membrane. The minimum inhibitory concentration (MIC) values of the CNGs (0.6 µg mL-1 against E. coli and S. aureus) remained almost the same against the bacteria after 20 passages; however, the MIC values increased significantly after treatment with silver nanoparticles, antibiotics, the bacteriostatic chlorhexidine, and especially gentamicin (approximately 140-fold). Additionally, the CNGs showed a negligible MIC value difference against the obtained resistant bacteria after acclimation to the abovementioned antimicrobial agents. The findings of this study unveil the development of antimicrobial CNGs as a sustainable solution to combat multidrug-resistant bacteria.
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Membrane damage as mechanism of photodynamic inactivation using Methylene blue and TMPyP in Escherichia coli and Staphylococcus aureus. Photochem Photobiol Sci 2022; 21:209-220. [PMID: 35061201 DOI: 10.1007/s43630-021-00158-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 12/11/2021] [Indexed: 12/22/2022]
Abstract
The worldwide threat of antibiotic resistance requires alternative strategies to fight bacterial infections. A promising approach to support conventional antibiotic therapy is the antimicrobial photodynamic inactivation (aPDI). The aim of this work was to show further insights into the antimicrobial photodynamic principle using two photosensitizers (PS) of different chemical classes, Methylene Blue (MB) and TMPyP, and the organisms Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive representatives. Planktonic cultures of both species were cultured under aerobic conditions for 24 h followed by treatment with MB or TMPyP at various concentrations for an incubation period of 10 min and subsequent irradiation for 10 min. Ability to replicate was evaluated by CFU assay. Accumulation of PS was measured using a spectrophotometer. The cytoplasmic membrane integrity was investigated by flow cytometry using SYBR Green and propidium iodide. In experiments on the replication ability of bacteria after photodynamic treatment with TMPyP or MB, a killing rate of 5 log10 steps of the bacteria was achieved. Concentration-dependent accumulation of both PS was shown by spectrophotometric measurements whereby a higher accumulation of TMPyP and less accumulation of MB was found for S. aureus as compared to E. coli. For the first time, a membrane-damaging effect of TMPyP and MB in both bacterial strains could be shown using flow cytometry analyses. Furthermore, we found that reduction of the replication ability occurs with lower concentrations than needed for membrane damage upon MB suggesting that membrane damage is not the only mechanism of aPDI using MB.
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Fox LJ, Kelly PP, Humphreys GJ, Waigh TA, Lu JR, McBain AJ. Assessing the risk of resistance to cationic biocides incorporating realism-based and biophysical approaches. J Ind Microbiol Biotechnol 2022; 49:kuab074. [PMID: 34718634 PMCID: PMC9113109 DOI: 10.1093/jimb/kuab074] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/27/2021] [Indexed: 12/30/2022]
Abstract
The control of microorganisms is a key objective in disease prevention and in medical, industrial, domestic, and food-production environments. Whilst the effectiveness of biocides in these contexts is well-evidenced, debate continues about the resistance risks associated with their use. This has driven an increased regulatory burden, which in turn could result in a reduction of both the deployment of current biocides and the development of new compounds and formulas. Efforts to balance risk and benefit are therefore of critical importance and should be underpinned by realistic methods and a multi-disciplinary approach, and through objective and critical analyses of the literature. The current literature on this topic can be difficult to navigate. Much of the evidence for potential issues of resistance generation by biocides is based on either correlation analysis of isolated bacteria, where reports of treatment failure are generally uncommon, or laboratory studies that do not necessarily represent real biocide applications. This is complicated by inconsistencies in the definition of the term resistance. Similar uncertainties also apply to cross-resistance between biocides and antibiotics. Risk assessment studies that can better inform practice are required. The resulting knowledge can be utilised by multiple stakeholders including those tasked with new product development, regulatory authorities, clinical practitioners, and the public. This review considers current evidence for resistance and cross-resistance and outlines efforts to increase realism in risk assessment. This is done in the background of the discussion of the mode of application of biocides and the demonstrable benefits as well as the potential risks.
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Affiliation(s)
- Laura J Fox
- Biological Physics, Department of Physics and Astronomy, Schuster Building, Faculty of Science and Engineering, University of Manchester, M13 9PL, UK
| | - Paul P Kelly
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
| | - Gavin J Humphreys
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
| | - Thomas A Waigh
- Biological Physics, Department of Physics and Astronomy, Schuster Building, Faculty of Science and Engineering, University of Manchester, M13 9PL, UK
| | - Jian R Lu
- Biological Physics, Department of Physics and Astronomy, Schuster Building, Faculty of Science and Engineering, University of Manchester, M13 9PL, UK
| | - Andrew J McBain
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
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Baena-Santillán ES, Piloni-Martini J, Rangel-Vargas E, Gómez-Aldapa CA, Sánchez-Gutiérrez M, Madrigal-Santillán EO, Castro-Rosas J. Comparison of the Antibacterial Activity and Effect on Membrane Permeability of Hibiscus Acid and a Commercial Chlorhexidine Mouthrinse Against Pathogenic Oral Bacteria and Determination of Hibiscus Acid Toxicity. J Med Food 2021; 25:324-328. [PMID: 34941430 DOI: 10.1089/jmf.2020.0207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The main aim of this study was to determine and compare the antimicrobial effect of hibiscus acid and a commercial 0.12% (w/v) chlorhexidine mouthrinse against Streptococcus mutans, Streptococcus sanguinis, Capnocytophaga gingivalis, and Staphylococcus aureus, and to determine the effect on bacterial cell membrane permeability and the toxicity of hibiscus acid in a mouse model. Hibiscus acid was obtained from acetone extract of Hibiscus sabdariffa calyces. Chlorhexidine (0.12% w/v) mouthrinse was purchased from a local pharmacy. The antimicrobial activity of hibiscus acid and mouthrinse were determined using the gel diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the solutions were determined using the broth dilution method. The effect on bacterial cell membrane permeability of hibiscus acid and mouthrinse was determined by crystal violet assay. The toxicity of hibiscus acid was investigated in a mouse model (registration number: UAEH2019-A1-S-8288). Hibiscus acid and mouthrinse showed antibacterial activity against all oral pathogenic bacteria. However, hibiscus acid showed a lower antibacterial effect compared with chlorhexidine mouthrinse. The MIC and MBC for hibiscus acid were 3 and 5 mg/mL, respectively, and was between 30 and 50 μg/mL for mouthrinse. The crystal violet test results indicate that hibiscus acid and mouthrinse alter the permeability of the bacterial membrane. Finally, hibiscus acid did not show toxicity in mouse studies.
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Affiliation(s)
- Elena S Baena-Santillán
- Institute of Agricultural Sciences, Rancho Universitario, Autonomous University of the Hidalgo State (UAEH), Tulancingo, Mexico.,Institute of Basic Sciences and Engineering, UAEH, City of Knowledge, Hidalgo, Mexico
| | - Javier Piloni-Martini
- Institute of Agricultural Sciences, Rancho Universitario, Autonomous University of the Hidalgo State (UAEH), Tulancingo, Mexico
| | | | - Carlos A Gómez-Aldapa
- Institute of Basic Sciences and Engineering, UAEH, City of Knowledge, Hidalgo, Mexico
| | | | | | - Javier Castro-Rosas
- Institute of Basic Sciences and Engineering, UAEH, City of Knowledge, Hidalgo, Mexico
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Efficacy of alpha-mangostin for antimicrobial activity against endodontopathogenic microorganisms in a multi-species bacterial-fungal biofilm model. Arch Oral Biol 2021; 133:105304. [PMID: 34775269 DOI: 10.1016/j.archoralbio.2021.105304] [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: 09/03/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To determine the activity of alpha-mangostin on preformed bacterial-fungal multi-species biofilms in vitro, and to ascertain the impact on metabolic activity, biofilm structure and viability. DESIGN Inhibitory concentrations (ICs) for alpha-mangostin against planktonic cultures of Candida albicans, Enterococcus faecalis, Lactobacillus rhamnosus, and Streptococcus gordonii were determined using a standard broth microdilution method. Single and multi-species (all species 1:1:1:1) biofilms were grown on polystyrene coverslips in Roswell Park Memorial Institute Medium for 48 h. The biofilms were then exposed to 0.2% (w/v) alpha-mangostin for 24 h. These concentrations were selected based on pilot experiments and the solubility of these compounds. 2% (v/v) chlorhexidine was used as a positive control and Roswell Park Memorial Institute Medium as a negative control. The metabolic activity of the biofilms after exposure was measured using metabolic (XTT) assays. Biofilms were visualised and quantified using fluorescent BacLight™ LIVE/DEAD staining. The biofilms were assessed for cell viability by culture and colony counting (CFU/mL). RESULTS 8 mg/L of alpha-mangostin was cidal against planktonic bacteria and 1000 mg/L for Candida. Alpha-mangostin was most active against L. rhamonosus biofilms and least active against C. albicans biofilm (metabolism inhibited by 99% and 78%, respectively). Alpha-mangostin exposure reduced the number of viable cells in the biofilms. CONCLUSION Alpha-mangostin inhibited the metabolic activity of bacterial-fungal biofilms effectively. The anti-biofilm activity of alpha-mangostin was comparable to chlorhexidine and thus has potential as a novel agent for endodontic therapy.
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Bergamini S, Bellei E, Generali L, Tomasi A, Bertoldi C. A Proteomic Analysis of Discolored Tooth Surfaces after the Use of 0.12% Chlorhexidine (CHX) Mouthwash and CHX Provided with an Anti-Discoloration System (ADS). MATERIALS 2021; 14:ma14154338. [PMID: 34361532 PMCID: PMC8347691 DOI: 10.3390/ma14154338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 07/27/2021] [Accepted: 07/30/2021] [Indexed: 02/07/2023]
Abstract
Chlorhexidine (CHX) is considered the gold standard for the chemical control of bacterial plaque and is often used after surgical treatment. However, CHX employment over an extended time is responsible for side effects such as the appearance of pigmentations on the teeth and tongue; the discoloration effects are less pronounced when using a CHX-based mouthwash with added an anti-discoloration system (ADS). The aim of this study was to evaluate, using one- and two-dimensional gel electrophoresis combined with mass spectrometry, the possible proteomic changes induced by CHX and CHX+ADS in the supragingival dental sites susceptible to a discoloration effect. The tooth surface collected material (TSCM) was obtained by curettage after resective bone surgery from three groups of patients following a supportive therapy protocol in which a mechanical control was combined with placebo rinses or CHX or a CHX+ADS mouthwash. The proteomic analysis was performed before surgery (basal conditions) and four weeks after surgery when CHX was used (or not) as chemical plaque control. Changes in the TSCM proteome were only revealed following CHX treatment: glycolytic enzymes, molecular chaperones and elongation factors were identified as more expressed. These changes were not detected after CHX+ADS treatment. An ADS could directly limit TSCM forming and also the CHX antiseptic effect reduces its ability to alter bacterial cell permeability. However, Maillard’s reaction produces high molecular weight molecules that change the surface properties and could facilitate bacterial adhesion.
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Rzycki M, Drabik D, Szostak-Paluch K, Hanus-Lorenz B, Kraszewski S. Unraveling the mechanism of octenidine and chlorhexidine on membranes: Does electrostatics matter? Biophys J 2021; 120:3392-3408. [PMID: 34214528 PMCID: PMC8391085 DOI: 10.1016/j.bpj.2021.06.027] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 04/26/2021] [Accepted: 06/22/2021] [Indexed: 11/20/2022] Open
Abstract
The increasing problem of antibiotic resistance in bacteria requires the development of new antimicrobial candidates. There are several well-known substances with commercial use, but their molecular mode of action is not fully understood. In this work, we focus on two commonly used antimicrobial agents from the detergent family—octenidine dichloride (OCT) and chlorhexidine digluconate (CHX). Both of them are reported to be agents selectively attacking the cell membrane through interaction inducing membrane disruption by emulsification. They are believed to present electrostatic selectivity toward charged lipids. In this study, we tested this hypothesis and revised previously proposed molecular mechanisms of action. Employing a variety of techniques such as molecular dynamics, ζ potential with dynamic light scattering, vesicle fluctuation spectroscopy, carboxyfluorescein leakage measurement, and fluorescence trimethylammonium-diphenylhexatriene- and diphenylhexatriene-based studies for determination of OCT and CHX membrane location, we performed experimental studies using two model membrane systems—zwitterionic PC and negatively charged PG (18:1/18:1):PC (16:0/18:1) 3:7, respectively. These studies were extended by molecular dynamics simulations performed on a three-component bacterial membrane model system to further test interactions with another negatively charged lipid, cardiolipin. In summary, our study demonstrated that detergent selectivity is far more complicated than supposed simple electrostatic interactions. Although OCT does disrupt the membrane, our results suggest that its primary selectivity was more linked to mechanical properties of the membrane. On the other hand, CHX did not disrupt membranes as a primary activity, nor did it show any sign of electrostatic selectivity toward negatively charged membranes at any stage of interactions, which suggests membrane disruption by influencing more discrete membrane properties.
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Affiliation(s)
- Mateusz Rzycki
- Department of Experimental Physics, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland; Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland.
| | - Dominik Drabik
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland; Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland
| | - Kamila Szostak-Paluch
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland; Research and Development Center, Regional Specialized Hospital, Wroclaw, Poland
| | - Beata Hanus-Lorenz
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland
| | - Sebastian Kraszewski
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wroclaw, Poland
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Alhenaki AM, Alqarawi FK, Tanveer SA, Alshahrani FA, Alshahrani A, AlHamdan EM, Alzahrani KM, Aldahiyan N, Naseem M, Vohra F, Abduljabbar T. Disinfection of acrylic denture resin polymer with Rose Bengal, Methylene blue and Porphyrin derivative in photodynamic therapy. Photodiagnosis Photodyn Ther 2021; 35:102362. [PMID: 34062305 DOI: 10.1016/j.pdpdt.2021.102362] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/19/2021] [Accepted: 05/24/2021] [Indexed: 11/26/2022]
Abstract
AIM The study aimed to assess the effect of in-vitro chlorhexidine and antimicrobial photodynamic therapy (aPDT) disinfection protocols against acrylic resin specimens colonized with S. mutans, S. aureus, E. coli, and C. albicans. MATERIAL AND METHODS Reference strains of S. mutans, S. aureus, E. coli, and C. albicans were tested. Sixteen blocks of acrylic specimens were prepared by heat-cure acrylic resin and contaminated by in-vitro biofilm growth. Specimens in group 1, group 2 and group 3 were treated with Rose Bengal (RB), methylene blue (MB) 500 mg/L and porphyrin derivative (PD) 5 ml respectively, for the sensitization of biofilms. All photosensitizers (PS) were activated by LED at different wavelength. CHX was prepared in sterile distilled water and applied for 60 s. Each contaminated specimen was sprayed on all its surfaces with the aforementioned photosensitizers and control CHX. One-way analysis of variance (ANOVA) model was used to test the effect of the treatments and Tukey multiple comparison tests to compare means OF CFU/mL (log10) for exposed E. coli, C. albicans, S aureus, and S. mutans RESULTS: Specimens treated with 0.12% CHX (control) demonstrated a significant reduction in CFU/mL (log10) for exposed E. coli; 2.04±0.07 CFU/mL, C. albicans; 2.09±0.85 CFU/mL, S aureus; 3.04±0.11 CFU/mL, and S. mutans; 2.54±0.91 CFU/mL. The intragroup comparison revealed E.coli did not exhibit a decrease in reduction CFU/mL (log10) when acrylic resin irradiated with RB 5 µm. Whereas, CFU/mL (log10) values of S.aureus; 3.62±0.68 and S.mutans; 3.41±0.13 plummeted (p<0.05). Intergroup comparison showed E.coli values to display comparable reduction when disinfected with MB 500 mg/L and 0.12% CHX; 3.16±0.34 and 2.04±0.07 CFU/mL (log10) (p<0.05). CONCLUSION Photosensitizers (RB, MB, PD) are selective in reducing bacterial count on acrylic resin blocks. CHX was found to be effective against all bacteria E.coli, C.albicans, S.aureus, and S.mutans at a concentration of 0.12%.
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Affiliation(s)
- Aasem M Alhenaki
- Prosthetic Dental Science Department, College Of Dentistry, King Saud University Riyadh, Saudi Arabia.
| | - Firas K Alqarawi
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
| | - Syeda A Tanveer
- Department of Oral Biology, College of Dentistry, Dow international Dental College. Karachi, Pakistan.
| | - Faris A Alshahrani
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
| | - Abdullah Alshahrani
- Prosthetic Dental Science Department, College Of Dentistry, King Saud University Riyadh, Saudi Arabia.
| | - Eman M AlHamdan
- Prosthetic Dental Science Department, College Of Dentistry, King Saud University Riyadh, Saudi Arabia.
| | - Khaled M Alzahrani
- Department of Prosthetic Dental sciences, College of Dentistry, Prince Sattam Bin AbdulAziz University, 11942 Alkharj Saudi Arabia.
| | - Nada Aldahiyan
- Post-Graduate Student. Department of Restorative Dental Science, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
| | - Mustafa Naseem
- Department of Community and Preventive Dental sciences, Dow International Dental College, Dow University of Health Sciences, Karachi, Pakistan.
| | - Fahim Vohra
- Prosthetic Dental Science Department, College Of Dentistry, King Saud University Riyadh, Saudi Arabia.
| | - Tariq Abduljabbar
- Prosthetic Dental Science Department, College Of Dentistry, King Saud University Riyadh, Saudi Arabia.
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Stawarz-Janeczek M, Kryczyk-Poprawa A, Muszyńska B, Opoka W, Pytko-Polończyk J. Disinfectants Used in Stomatology and SARS-CoV-2 Infection. Eur J Dent 2021; 15:388-400. [PMID: 33694135 PMCID: PMC8184310 DOI: 10.1055/s-0041-1724154] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Effective disinfection is a basic procedure in medical facilities, including those conducting dental surgeries, where treatments for tissue discontinuity are also performed, as it is an important element of infection prevention. Disinfectants used in dentistry and dental and maxillofacial surgery include both inorganic (hydrogen peroxide, sodium chlorite-hypochlorite) and organic compounds (ethanol, isopropanol, peracetic acid, chlorhexidine, eugenol). Various mechanisms of action of disinfectants have been reported, which include destruction of the structure of bacterial and fungal cell membranes; damage of nucleic acids; denaturation of proteins, which in turn causes inhibition of enzyme activity; loss of cell membrane integrity; and decomposition of cell components. This article discusses the most important examples of substances used as disinfectants in dentistry and presents the mechanisms of their action with particular focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The search was conducted in ScienceDirect, PubMed, and Scopus databases. The interest of scientists in the use of disinfectants in dental practice is constantly growing, which results in the increasing number of publications on disinfection, sterilization, and asepsis. Many disinfectants often possess several of the abovementioned mechanisms of action. In addition, disinfectant preparations used in dental practice either contain one compound or are frequently a mixture of active compounds, which increases their range and effectiveness of antimicrobial action. Currently available information on disinfectants that can be used to prevent SARS-CoV-2 infection in dental practices was summarized.
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Affiliation(s)
- Magdalena Stawarz-Janeczek
- Department of Integrated Dentistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland
| | - Agata Kryczyk-Poprawa
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
| | - Bożena Muszyńska
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
| | - Włodzimierz Opoka
- Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
| | - Jolanta Pytko-Polończyk
- Department of Integrated Dentistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland
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Alves D, Borges P, Grainha T, Rodrigues CF, Pereira MO. Tailoring the immobilization and release of chlorhexidine using dopamine chemistry to fight infections associated to orthopedic devices. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 120:111742. [PMID: 33545884 DOI: 10.1016/j.msec.2020.111742] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 11/03/2020] [Accepted: 11/17/2020] [Indexed: 11/30/2022]
Abstract
A crucial factor in the pathogenesis of orthopedics associated infections is that bacteria do not only colonize the implant surface but also the surrounding tissues. This study aimed to engineer an antimicrobial release coating for stainless steel (SS) surfaces, to impart them with the ability to prevent Staphylococci colonization. Chlorhexidine (CHX) was immobilized using two polydopamine (pDA)-based approaches: a one-pot synthesis, where CHX is dissolved together with dopamine before its polymerization; and a two-step methodology, comprising the deposition of a pDA layer to which CHX is immobilized. To modulate CHX release, an additional layer of pDA was also added for both strategies. Immobilization of CHX using a one-step approach yielded surfaces with a more homogenous coating and less roughness than the other strategies. The amount of released CHX was lower for the one-step approach, as opposed to the two-step approach yielding the higher release, which could be decreased by applying an outward layer of pDA. Both one and two-step approaches provided the surfaces with the ability to prevent bacterial colonization of the surface itself and kill most of bacteria in the bulk phase up to 10 days. This long-term antimicrobial performance alluded a stable and enduring immobilization of CHX. In terms of biocompatibility, the amount of CHX released from the one-step approach did not compromise the growth of mammalian cells, contrary to the two-step strategy. Additionally, the few bacteria that managed to adhere to surfaces modified with one-step approach did not show evidence of resistance towards CHX. Overall data underline that one-step immobilization of CHX holds great potential to be further applied in the fight against orthopedic devices associated infections.
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Affiliation(s)
- Diana Alves
- CEB - Centre of Biological Engineering, LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
| | - Patrick Borges
- CEB - Centre of Biological Engineering, LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - Tânia Grainha
- CEB - Centre of Biological Engineering, LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - Célia F Rodrigues
- CEB - Centre of Biological Engineering, LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
| | - Maria Olívia Pereira
- CEB - Centre of Biological Engineering, LIBRO - Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
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Genetic and physiological effects of subinhibitory concentrations of oral antimicrobial agents on Streptococcus mutans biofilms. Microb Pathog 2020; 150:104669. [PMID: 33278519 DOI: 10.1016/j.micpath.2020.104669] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 08/01/2020] [Accepted: 11/26/2020] [Indexed: 11/22/2022]
Abstract
Streptococcus mutans is the main etiological agent of dental caries because of its capacity to adhere to enamel structure and form biofilms. This study aimed to evaluate the effects of the anticariogenic agents - sodium fluoride (NaF) and chlorhexidine (CHX) - at levels below minimum inhibitory concentrations (sub-MICs) on the growth of planktonic cells and biofilms and on the expression of vicR and covR genes associated with the regulation of biofilm formation. MICs and minimum bactericidal concentrations (MBCs) of NaF and CHX were determined for S. mutans strains ATCC25175, UA159 and 3VF2. Growth curves were constructed for planktonic cells cultured in brain heart infusion (BHI) broth supplemented with NaF (0.125-0.75MIC) or CHX (0.25-0.75MIC). Biofilm formation assays were performed in microplates containing CHX or NaF at 0.5-1.0MIC and stained with violet crystal. Quantitative polymerase chain reaction determined the alterations in covR and vicR expression in cells exposed to antimicrobials at sub-MIC levels. NaF and CHX at sub-MIC levels affected the growth of planktonic cells of all three S. mutans strains, depending on the concentration tested. The biofilm formation in UA159 and 3VF2 was reduced by NaF at concentrations ≥0.5 MIC, while that of ATCC 25175 was reduced significantly irrespective of dose. In contrast, UA159 and 3VF2 biofilms were not affected by CHX at these levels, whereas those of ATCC 25175 were reduced significantly at all concentrations tested. Under sub-MIC conditions, CHX and (to a lesser degree) NaF increased vicR and covR expression in all three strains, although there were large differences between strains and treatment conditions employed. CHX and NaF at sub-MIC levels influence on the growth of S. mutans in planktonic and biofilm conditions and on transcript levels of biofilm-associated genes vicR and covR, in a dose-dependent manner.
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AlQranei MS, Balhaddad AA, Melo MAS. The burden of root caries: Updated perspectives and advances on management strategies. Gerodontology 2020; 38:136-153. [PMID: 33236462 DOI: 10.1111/ger.12511] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/26/2020] [Accepted: 11/02/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Root caries has gained much attention in the last few years. As the world's population is ageing and people currently tend to retain more teeth compared with older generations, there is an increased prevalence of periodontal disease and gingival recession, which may accelerate the onset of root caries. OBJECTIVE This review aims to summarise recent findings related to the diagnosis, prevention and treatment of root caries. MATERIALS AND METHODS MEDLINE (OVID) and Scopus (Elsevier) searches were performed to identify and discuss articles that address the pathogenicity and clinical management of root caries. RESULTS Root caries is a multifactorial disease. Cariogenic species involved in root caries are less dependent on carbohydrates since collagen degradation inside the dentinal tubules can provide nutrients and microcavities for the invading microorganisms. Furthermore, the root surface has fewer minerals in comparison with enamel, which may accelerate the onset of demineralisation. Root caries could be prevented by patient education, modification of risk factors, and the use of in-office and home remineralisation tools. The use of non-invasive approaches to control root caries is recommended, as the survival rate of root caries restorations is poor. When plaque control is impossible and a deep/large cavity is present, glass ionomer or resin-based restorations can be placed. CONCLUSION The assessment of root carious lesions is critical to determine the lesion activity and the required intervention. Dental practitioners should also be aware of different prevention and treatment approaches to design optimum oral health care for root caries-affected patients.
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Affiliation(s)
- Mohammed S AlQranei
- Department of Preventive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Abdulrahman A Balhaddad
- Department of Restorative Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mary A S Melo
- Division of Operative Dentistry, Department of General Dentistry, University of Maryland Dental School, Baltimore, MD, USA
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41
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Kholina EG, Kovalenko IB, Bozdaganyan ME, Strakhovskaya MG, Orekhov PS. Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes. J Phys Chem B 2020; 124:8593-8600. [PMID: 32896131 DOI: 10.1021/acs.jpcb.0c07212] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.
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Affiliation(s)
- E G Kholina
- Department of Biology, Lomonosov Moscow State University, Moscow 119234, Russia
| | - I B Kovalenko
- Department of Biology, Lomonosov Moscow State University, Moscow 119234, Russia.,Sechenov University, Moscow 119991, Russia.,Astrakhan State University, Astrakhan 414056, Russia.,Peoples' Friendship University of Russia (RUDN University), Moscow 117198, Russia
| | - M E Bozdaganyan
- Department of Biology, Lomonosov Moscow State University, Moscow 119234, Russia.,N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia.,Moscow Polytechnic University, Moscow 107023, Russia
| | - M G Strakhovskaya
- Department of Biology, Lomonosov Moscow State University, Moscow 119234, Russia.,Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical and Biological Agency of Russia, Moscow 115682, Russia
| | - P S Orekhov
- Department of Biology, Lomonosov Moscow State University, Moscow 119234, Russia.,Sechenov University, Moscow 119991, Russia.,Moscow Institute of Physics and Technology, Dolgoprudny 141700, Russia
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42
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Addressing the challenges in antisepsis: focus on povidone iodine. Int J Antimicrob Agents 2020; 56:106064. [DOI: 10.1016/j.ijantimicag.2020.106064] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Revised: 05/21/2020] [Accepted: 06/21/2020] [Indexed: 12/15/2022]
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Alveolar iodine tampon packing after impacted third molar surgery improves oral health-related quality of life and postoperative sequela: a randomized study. Oral Maxillofac Surg 2020; 25:181-190. [PMID: 32862256 PMCID: PMC8121736 DOI: 10.1007/s10006-020-00898-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 08/18/2020] [Indexed: 11/17/2022]
Abstract
Objective The aim of this study was to evaluate the effect of an iodine tampon on postoperative discomfort after surgical removal of a mandibular third molar. Material and methods Patients were randomly assigned to two groups: one group received an alveolar iodine-containing tampon in the extraction socket (N = 44), and the other group used a disposable syringe (Monoject®) to rinse the wound (N = 43). Postoperative discomfort was assessed with the Oral Health Impact Profile-14 (OHIP-14) questionnaire, Pain Intensity Numerical Rating Scale (PI-NRS), and questions about self-care and discomfort. Results This study included 87 patients (52 women and 35 men) with an average age of 26.47 years (SD, 6.36). The mean OHIP-14 sum scores were significantly lower in the iodine tampon group compared with the Monoject® syringe group. Mean PI-NRS scores significantly differed between the iodine tampon group (3.33; SE, 0.27) and Monoject® syringe group (4.46; SE, 0.27) (F (1, 85) = 8.16, p < 0.01), with no interaction effect between time and PI-NRS (F (6, 510) = 1.26, p = 0.28). Patients in the iodine tampon group reported less postoperative discomfort. Conclusions Insertion of an iodine-containing tampon in the postoperative socket reduced the pain and impact on oral health-related quality of life during the first postoperative week and positively influenced postoperative sequelae.
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Zhu J, Huang Y, Hu C, Huang Y, Chen M, He X, Zhang Y, Wang Y, Chen Y. Inhibitory Effects and Mechanism of the Combined Use of α-Helical Peptides HPRP-A1/HPRP-A2 and Chlorhexidine Acetate Against Bacterial and Fungal Biofilms. Int J Pept Res Ther 2020. [DOI: 10.1007/s10989-020-10102-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Fernandez M, Paulucci NS, Reynoso E, Morales GM, Agostini E, González PS. Morphological and structural response of Bacillus sp. SFC 500-1E after Cr(VI) and phenol treatment. J Basic Microbiol 2020; 60:679-690. [PMID: 32378234 DOI: 10.1002/jobm.202000076] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/04/2020] [Accepted: 04/22/2020] [Indexed: 11/10/2022]
Abstract
Bacillus sp. SFC 500-1E, a bacterial strain isolated from tannery sediments, is able to remove Cr(VI) and simultaneously tolerate high concentrations of phenol. In this study, we used high-resolution microscopies, fluorescence polarization techniques, and several biochemical approaches to improve our understanding about the adaptive mechanisms of this strain to survive in the presence of Cr(VI) and phenol, both individually and simultaneously. Among adaptive strategies developed by Bacillus sp. SFC 500-1E, an increase in bacterial size, such as length, width, and height, and ultrastructural alterations, such as electron-dense precipitates, the presence of exopolymers, and cell lysis, are noteworthy. The exopolymers observed were consistent with the extensive biofilm formation and exopolysaccharides and extracellular protein quantification. At the cell membrane level, a rapid rigidity was induced in Cr(VI) + phenol treatment. This effect was counteracted after 16 h by changes at the level of phospholipids, mainly in the composition of fatty acids (FAs); in particular, an increase in the unsaturated fatty acid/saturated fatty acid ratio was detected. This study shows evidence of some adaptive responses displayed by Bacillus sp. SFC 500-1E, which allows it to survive in stressful conditions.
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Affiliation(s)
- Marilina Fernandez
- Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Biotecnología Ambiental y Salud (INBIAS), Río Cuarto, Córdoba, Argentina
| | - Natalia S Paulucci
- Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Biotecnología Ambiental y Salud (INBIAS), Río Cuarto, Córdoba, Argentina
| | - Eugenia Reynoso
- Departamento de Química- FCEFQyN, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Río Cuarto, Córdoba, Argentina
| | - Gustavo M Morales
- Departamento de Química- FCEFQyN, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados (IITEMA), Río Cuarto, Córdoba, Argentina
| | - Elizabeth Agostini
- Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Biotecnología Ambiental y Salud (INBIAS), Río Cuarto, Córdoba, Argentina
| | - Paola S González
- Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Río Cuarto, Córdoba, Argentina.,CONICET-UNRC, Instituto de Biotecnología Ambiental y Salud (INBIAS), Río Cuarto, Córdoba, Argentina
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O'Donnell VB, Thomas D, Stanton R, Maillard JY, Murphy RC, Jones SA, Humphreys I, Wakelam MJO, Fegan C, Wise MP, Bosch A, Sattar SA. Potential Role of Oral Rinses Targeting the Viral Lipid Envelope in SARS-CoV-2 Infection. FUNCTION 2020; 1:zqaa002. [PMID: 33215159 PMCID: PMC7239187 DOI: 10.1093/function/zqaa002] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/04/2020] [Accepted: 05/08/2020] [Indexed: 01/06/2023] Open
Abstract
Emerging studies increasingly demonstrate the importance of the throat and salivary glands as sites of virus replication and transmission in early COVID-19 disease. SARS-CoV-2 is an enveloped virus, characterized by an outer lipid membrane derived from the host cell from which it buds. While it is highly sensitive to agents that disrupt lipid biomembranes, there has been no discussion about the potential role of oral rinsing in preventing transmission. Here, we review known mechanisms of viral lipid membrane disruption by widely available dental mouthwash components that include ethanol, chlorhexidine, cetylpyridinium chloride, hydrogen peroxide, and povidone-iodine. We also assess existing formulations for their potential ability to disrupt the SARS-CoV-2 lipid envelope, based on their concentrations of these agents, and conclude that several deserve clinical evaluation. We highlight that already published research on other enveloped viruses, including coronaviruses, directly supports the idea that oral rinsing should be considered as a potential way to reduce transmission of SARS-CoV-2. Research to test this could include evaluating existing or specifically tailored new formulations in well-designed viral inactivation assays, then in clinical trials. Population-based interventions could be undertaken with available mouthwashes, with active monitoring of outcome to determine efficacy. This is an under-researched area of major clinical need.
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Affiliation(s)
| | - David Thomas
- Systems Immunity Research Institute.,School of Dentistry
| | | | - Jean-Yves Maillard
- Systems Immunity Research Institute.,School of Pharmacy and Pharmaceutical Sciences, Cardiff University, CF14 4XN, UK
| | - Robert C Murphy
- Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA
| | - Simon A Jones
- Systems Immunity Research Institute.,School of Medicine
| | - Ian Humphreys
- Systems Immunity Research Institute.,School of Medicine
| | | | | | - Matt P Wise
- University Hospital of Wales, Cardiff, CF14 4XW, UK
| | - Albert Bosch
- Enteric Virus Laboratory, University of Barcelona, 08028 Barcelona, Spain
| | - Syed A Sattar
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5 Canada
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Chen H, Tang Y, Weir MD, Gao J, Imazato S, Oates TW, Lei L, Wang S, Hu T, Xu HHK. Effects of S. mutans gene-modification and antibacterial monomer dimethylaminohexadecyl methacrylate on biofilm growth and acid production. Dent Mater 2019; 36:296-309. [PMID: 31839202 DOI: 10.1016/j.dental.2019.12.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 08/17/2019] [Accepted: 12/02/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Antibacterial quaternary ammonium monomers (QAMs) are used in resins. The rnc gene in Streptococcus mutans (S. mutans) plays a key role in resisting antibiotics. The objectives of this study were to investigate for the first time: (1) the effects of rnc deletion on S. mutans biofilms and acid production; (2) the combined effects of rnc deletion with dimethylaminohexadecyl methacrylate (DMAHDM) on biofilm-inhibition efficacy. METHODS Parent S. mutans strain UA159 (ATCC 700610) and the rnc-deleted S. mutans were used. Bacterial growth, minimum inhibitory concentration (MIC), and minimal bactericidal concentration (MBC) were measured to analyze the bacterial susceptibility of the parent and rnc-deleted S. mutans against DMAHDM, with the gold-standard chlorhexidine (CHX) as control. Biofilm biomass, polysaccharide and lactic acid production were measured. RESULTS The drug-susceptibility of the rnc-deleted S. mutans to DMAHDM or CHX was 2-fold higher than parent S. mutans. The drug-susceptibility did not increase after 10 passages (p < 0.05). Deleting the rnc gene increased the biofilm susceptibility to DMAHDM or CHX by 2-fold. The rnc-deletion in S. mutans reduced biofilm biomass, polysaccharide and lactic acid production, even at no drugs. DMAHDM was nearly 40 % more potent than the gold-standard CHX. The combination of rnc deletion+DMAHDM treatment achieved the greatest reduction in biofilm biomass, polysaccharide synthesis, and lactic acid production. SIGNIFICANCE Gene modification by deleting the rnc in S. mutans reduced the biofilm growth and acid production, and the rnc deletion+DMAHDM method showed the greatest biofilm-inhibition efficacy, for the first time. The dual strategy of antibacterial monomer+bacterial gene modification shows great potential to control biofilms and inhibit caries.
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Affiliation(s)
- Hong Chen
- State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA
| | - Yunhao Tang
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Michael D Weir
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA
| | - Jianghong Gao
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Preventive Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Satoshi Imazato
- Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan
| | - Thomas W Oates
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA
| | - Lei Lei
- State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Suping Wang
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Department of Operative Dentistry and Endodontics & Periodontics and Stomatology Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
| | - Tao Hu
- State Key Laboratory of Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
| | - Hockin H K Xu
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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2CS-CHX T Operon Signature of Chlorhexidine Tolerance among Enterococcus faecium Isolates. Appl Environ Microbiol 2019; 85:AEM.01589-19. [PMID: 31562170 DOI: 10.1128/aem.01589-19] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Accepted: 09/20/2019] [Indexed: 11/20/2022] Open
Abstract
Chlorhexidine (CHX) is a broad-spectrum antiseptic widely used in community and clinical contexts for many years that has recently acquired higher relevance in nosocomial infection control worldwide. Despite this, CHX tolerance among Enterococcus faecium bacteria, representing one of the leading agents causing nosocomial infections, has been poorly understood. This study provides new phenotypic and molecular data for better identification of CHX-tolerant E. faecium subpopulations in community and clinical contexts. The chlorhexidine MIC (MICCHX) distribution of 106 E. faecium isolates suggested the occurrence of tolerant subpopulations in diverse sources (human, animal, food, environment) and phylogenomic backgrounds (clades A1/A2/B), with predominance in clade A1. They carried a specific variant of the 2CS-CHXT operon, identified here. It encodes glucose and amino acid-polyamine-organocation family transporters, besides the DNA-binding response regulator ChtR, with a P102H mutation previously described only in CHX-tolerant clade A1 E. faecium, and the ChtS sensor. 2CS-CHXT seems to be associated with three regulons modulating diverse bacterial biological functions. Combined data from normal MIC distribution and 2CS-CHXT operon characterization support a tentative epidemiological cutoff (ECOFF) of 8 mg/liter to CHX, which is useful to detect tolerant E. faecium populations in future surveillance studies. The spread of tolerant E. faecium in diverse epidemiological backgrounds calls for the prudent use of CHX in multiple contexts.IMPORTANCE Chlorhexidine is one of the substances included in the World Health Organization's list of essential medicines, which comprises the safest and most effective medicines needed in global health systems. Although it has been widely applied as a disinfectant and antiseptic in health care (skin, hands, mouthwashes, eye drops) since the 1950s, its use in hospitals to prevent nosocomial infections has increased worldwide in recent years. Here, we provide a comprehensive study on chlorhexidine tolerance among strains of Enterococcus faecium, one of the leading nosocomial agents worldwide, and identify a novel 2CS-CHXT operon as a signature of tolerant strains occurring in diverse phylogenomic groups. Our data allowed for the proposal of a tentative epidemiological cutoff of 8 mg/liter, which is useful to detect tolerant E. faecium populations in surveillance studies in community and clinical contexts. The prediction of 2CS-CHXT regulons will also facilitate the design of future experimental studies to better uncover chlorhexidine tolerance among E. faecium bacteria.
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Zhu J, Huang Y, Chen M, Hu C, Chen Y. Functional Synergy Of Antimicrobial Peptides And Chlorhexidine Acetate Against Gram-Negative/Gram-Positive Bacteria And A Fungus In Vitro And In Vivo. Infect Drug Resist 2019; 12:3227-3239. [PMID: 31686873 PMCID: PMC6800562 DOI: 10.2147/idr.s218778] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 09/25/2019] [Indexed: 01/10/2023] Open
Abstract
Background and purpose To reduce the resistance and allergic reaction to chlorhexidine acetate (CHA) in the current treatment of (Bacterial vaginosis) BV and (vulvovaginal candidiasis) VVC in female vaginitis. In this study, the antimicrobial activities and mechanism of action of the synergistic effects of antimicrobial peptides (AMPs) HPRP-A1 and HPRP-A2, and CHA, against Gram-negative and Gram-positive bacteria, and one fungus Candida albicans (C. albicans) were investigated in vitro and in mouse and rat vaginitis infection models in vivo. Results HPRP-A1, HPRP-A2 and CHA showed significant synergistic effects on the antimicrobial activities against different Gram-negative and Gram-positive bacteria and C. albicans. The combined application of HPRP-A2 and CHA exhibited strong synergistic effects in the mouse and rat vaginitis models caused by bacteria or C. albicans. Conclusion This study may prompt the development of new drug combinations against vaginitis infections, including mixed bacterial and fungal infections and multi-drug-resistant infections.
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Affiliation(s)
- Jie Zhu
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, People's Republic of China.,College of Life Sciences, Jilin University, Changchun, People's Republic of China
| | - Yibing Huang
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, People's Republic of China.,College of Life Sciences, Jilin University, Changchun, People's Republic of China
| | - Mingxia Chen
- Jiangsu ProteLight Pharmaceutical & Biotechnology Co., Ltd., Jiangyin, People's Republic of China
| | - Cuihua Hu
- International Research Centre for Nano Handling and Manufacturing, Changchun University of Science and Technology, Changchun, People's Republic of China
| | - Yuxin Chen
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, People's Republic of China.,College of Life Sciences, Jilin University, Changchun, People's Republic of China.,Jiangsu ProteLight Pharmaceutical & Biotechnology Co., Ltd., Jiangyin, People's Republic of China
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50
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Spontaneously Arising Streptococcus mutans Variants with Reduced Susceptibility to Chlorhexidine Display Genetic Defects and Diminished Fitness. Antimicrob Agents Chemother 2019; 63:AAC.00161-19. [PMID: 31036688 DOI: 10.1128/aac.00161-19] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 04/20/2019] [Indexed: 01/10/2023] Open
Abstract
Chlorhexidine (CHX) has been used to control dental caries caused by acid-tolerant bacteria such as Streptococcus mutans since the 1970s. Repeat CHX exposure for other bacterial species results in the development of variants with reduced susceptibility that also become more resistant to other antimicrobials. It has not been tested if such variants arise when streptococci are exposed to CHX. Here, we passaged S. mutans in increasing concentrations of CHX and isolated spontaneously arising reduced susceptibility variants (RSVs) from separate lineages that have MICs that are up to 3-fold greater than the parental strain. The RSVs have increased growth rates at neutral pH and under acidic conditions in the presence of CHX but accumulate less biomass in biofilms. RSVs display higher MICs for daptomycin and clindamycin but increased sensitivity to dental-relevant antimicrobials triclosan and sodium fluoride. Plate-based assays for competition with health-associated oral streptococci revealed decreased bacteriocin production by the RSVs, increased sensitivity to hydrogen peroxide, and diminished competitive fitness in a human-derived ex vivo biofilm consortium. Whole-genome sequencing identified common single nucleotide polymorphisms (SNPs) within a diacylglycerol kinase homolog and a glycolipid synthesis enzyme, which could alter the accumulation of lipoteichoic acids and other envelope constituents, as well as a variety of mutations in other genes. Collectively, these findings confirm that S. mutans and likely other streptococci can develop tolerance to CHX but that increased tolerance comes at a fitness cost, such that CHX-induced variants that spontaneously arise in the human oral cavity may not persist.
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