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      The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota

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      1 , 2 , 3 , 4 , , 5 , 6 , 5 , 6 ,
      Microbiome
      BioMed Central

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          Abstract

          In the cervicovaginal environment, the production of hydrogen peroxide (H 2O 2) by vaginal Lactobacillus spp. is often mentioned as a critical factor to the in vivo vaginal microbiota antimicrobial properties. We present several lines of evidence that support the implausibility of H 2O 2 as an “in vivo” contributor to the cervicovaginal milieu antimicrobial properties. An alternative explanation is proposed, supported by previous reports ascribing protective and antimicrobial properties to other factors produced by Lactobacillus spp. capable of generating H 2O 2. Under this proposal, lactic acid rather than H 2O 2 plays an important role in the antimicrobial properties of protective vaginal Lactobacillus spp. We hope this commentary will help future research focus on more plausible mechanisms by which vaginal Lactobacillus spp. exert their antimicrobial and beneficial properties, and which have in vivo and translational relevance.

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          Most cited references43

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          Temporal dynamics of the human vaginal microbiota.

          Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
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            Antibacterial activities of bacteriocins: application in foods and pharmaceuticals

            Bacteriocins are a kind of ribosomal synthesized antimicrobial peptides produced by bacteria, which can kill or inhibit bacterial strains closely-related or non-related to produced bacteria, but will not harm the bacteria themselves by specific immunity proteins. Bacteriocins become one of the weapons against microorganisms due to the specific characteristics of large diversity of structure and function, natural resource, and being stable to heat. Many recent studies have purified and identified bacteriocins for application in food technology, which aims to extend food preservation time, treat pathogen disease and cancer therapy, and maintain human health. Therefore, bacteriocins may become a potential drug candidate for replacing antibiotics in order to treat multiple drugs resistance pathogens in the future. This review article summarizes different types of bacteriocins from bacteria. The latter half of this review focuses on the potential applications in food science and pharmaceutical industry.
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              Vaginal pH and Microbicidal Lactic Acid When Lactobacilli Dominate the Microbiota

              Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure. The pH of samples was measured by microelectrode immediately after collection and under a physiological vaginal concentration of CO2. Commercial enzymatic assays of total lactate and total acetate concentrations were validated for use in CVF, and compared to the more usual HPLC method. The average pH of the CVF samples was 3.5 ± 0.3 (mean ± SD), range 2.8-4.2, and the average total lactate was 1.0% ± 0.2% w/v; this is a five-fold higher average hydrogen ion concentration (lower pH) and a fivefold higher total lactate concentration than in the prior literature. The microbicidal form of lactic acid (protonated lactic acid) was therefore eleven-fold more concentrated, and a markedly more potent microbicide, than indicated by prior research. This suggests that when lactobacilli dominate the vaginal microbiota, women have significantly more lactic acid-mediated protection against infections than currently believed. Our results invite further evaluations of the prophylactic and therapeutic actions of vaginal lactic acid, whether provided in situ by endogenous lactobacilli, by probiotic lactobacilli, or by products that reinforce vaginal lactic acid.
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                Author and article information

                Contributors
                gilda.tachedjian@burnet.edu.au
                DOHanlon@som.umaryland.edu
                jravel@som.umaryland.edu
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                6 February 2018
                6 February 2018
                2018
                : 6
                : 29
                Affiliations
                [1 ]ISNI 0000 0001 2224 8486, GRID grid.1056.2, Disease Elimination Program, Life Sciences Discipline, , Burnet Institute, ; 85 Commercial Rd, Melbourne, Victoria 3004 Australia
                [2 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Department of Microbiology, , Monash University, ; Clayton, VIC 3168 Australia
                [3 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Microbiology and Immunology, , The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, ; Melbourne, VIC 3010 Australia
                [4 ]ISNI 0000 0001 2163 3550, GRID grid.1017.7, School of Science, College of Science, Engineering and Health, , RMIT University, ; Melbourne, Victoria 3000 Australia
                [5 ]ISNI 0000 0001 2175 4264, GRID grid.411024.2, Institute for Genome Sciences, , University of Maryland School of Medicine, ; 801 West Baltimore Street, Baltimore, MD 21201 USA
                [6 ]ISNI 0000 0001 2175 4264, GRID grid.411024.2, Department of Microbiology and Immunology, , University of Maryland School of Medicine, ; Baltimore, MD 21201 USA
                Author information
                http://orcid.org/0000-0002-0851-2233
                Article
                418
                10.1186/s40168-018-0418-3
                5801833
                29409534
                4a84dec6-33eb-456f-8500-27ac612af89c
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 January 2018
                : 30 January 2018
                Funding
                Funded by: National Health and Medical Research Council (AU)
                Award ID: APP1117748
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: APP1088564
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: U19AI084044
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000056, National Institute of Nursing Research;
                Award ID: R01NR015495
                Award Recipient :
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                © The Author(s) 2018

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