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      Glycerol Monolaurate (GML) and a Nonaqueous Five-Percent GML Gel Kill Bacillus and Clostridium Spores

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      a , , a , a , a , a
      (Solicited external reviewer), (Solicited external reviewer), (Solicited external reviewer)
      mSphere
      American Society for Microbiology
      Bacillus, Clostridium, endospores, glycerol monolaurate

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          Abstract

          Bacillus and Clostridium spores are known to be highly resistant to killing, persisting on environmental and human body surfaces for long periods of time. In favorable environments, these spores may germinate and cause human diseases. It is thus important to identify agents that can be used on both environmental and human skin and mucosal surfaces and that are effective in killing spores. We previously showed that the fatty acid monoester glycerol monolaurate (GML) kills stationary-phase cultures of Bacillus anthracis. Since such cultures are likely to contain spores, it is possible that GML and a human-use-approved GML nonaqueous gel would kill Bacillus and Clostridium spores. The significance of our studies is that we have identified GML, and, to a greater extent, GML solubilized in a nonaqueous gel, as effective in killing spores from both bacterial genera.

          ABSTRACT

          Glycerol monolaurate is a broadly antimicrobial fatty acid monoester, killing bacteria, fungi, and enveloped viruses. The compound kills stationary-phase cultures of Bacillus anthracis, suggesting that the molecule may kill spores. In this study, we examined the ability of glycerol monolaurate alone or solubilized in a nonaqueous gel to kill vegetative cells and spores of aerobic B. anthracis, B. subtilis, and B. cereus and anaerobic Clostridium perfringens and Clostridium ( Clostridioides) difficile. Glycerol monolaurate alone was bactericidal for all five organisms tested. Glycerol monolaurate alone was effective in killing spores. When solubilized in a nonaqueous gel, the glycerol monolaurate gel was bactericidal for all spores tested. The data suggest that glycerol monolaurate nonaqueous gel could be effective in decontaminating environmental and body surfaces, such as skin.

          IMPORTANCE Bacillus and Clostridium spores are known to be highly resistant to killing, persisting on environmental and human body surfaces for long periods of time. In favorable environments, these spores may germinate and cause human diseases. It is thus important to identify agents that can be used on both environmental and human skin and mucosal surfaces and that are effective in killing spores. We previously showed that the fatty acid monoester glycerol monolaurate (GML) kills stationary-phase cultures of Bacillus anthracis. Since such cultures are likely to contain spores, it is possible that GML and a human-use-approved GML nonaqueous gel would kill Bacillus and Clostridium spores. The significance of our studies is that we have identified GML, and, to a greater extent, GML solubilized in a nonaqueous gel, as effective in killing spores from both bacterial genera.

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          Glycerol monolaurate prevents mucosal SIV transmission

          While there has been great progress in treating HIV-1 infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2–4. Nonetheless, studies of vaginal transmission in the SIV-rhesus macaque model point to opportunities in the earliest stages of infection where a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5, 6. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α, plasmacytoid dendritic cells and CCR5+cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruit CD4+T cells to fuel this obligate expansion. We then show that glycerol monolaurate, a widely used antimicrobial compound 7 with inhibitory activity against production of MIP-3α and other proinflammatory cytokines8, can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This novel approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for development of effective interventions to block HIV-1 mucosal transmission.
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            Ecology and genomics of Bacillus subtilis.

            Bacillus subtilis is a remarkably diverse bacterial species that is capable of growth within many environments. Recent microarray-based comparative genomic analyses have revealed that members of this species also exhibit considerable genomic diversity. The identification of strain-specific genes might explain how B. subtilis has become so broadly adapted. The goal of identifying ecologically adaptive genes could soon be realized with the imminent release of several new B. subtilis genome sequences. As we embark upon this exciting new era of B. subtilis comparative genomics we review what is currently known about the ecology and evolution of this species.
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              Biology of Clostridium difficile: implications for epidemiology and diagnosis.

              Clostridium difficile is an anaerobic, spore-forming, gram-positive rod that causes a spectrum of antibiotic-associated colitis through the elaboration of two large clostridial toxins and other virulence factors. Since its discovery in 1978 as the agent responsible for pseudomembranous colitis, the organism has continued to evolve into an adaptable, aggressive, hypervirulent strain. Advances in molecular methods and improved animal models have facilitated an understanding of how this organism survives in the environment, adapts to the gastrointestinal tract of animals and humans, and accomplishes its unique pathogenesis. The advances in microbiology have been accompanied by some important clinical observations including increased rates of C. difficile infection, increased virulence, and multiple outbreaks. The major new risk is fluoroquinolone use; there is also an association with proton pump inhibitors and increased recognition of cases in outpatients, pediatric patients, and patients without recent antibiotic use. The combination of more aggressive strains with mobile genomes in a setting of an expanded pool of individuals at risk has refocused attention on and challenged assumptions regarding diagnostic gold standards. Future research is likely to build upon the advancements in phylogenetics to create novel strategies for diagnosis, treatment, and prevention.
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                Author and article information

                Contributors
                Role: Editor
                Role: Solicited external reviewer
                Role: Solicited external reviewer
                Role: Solicited external reviewer
                Journal
                mSphere
                mSphere
                msph
                msph
                mSphere
                mSphere
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2379-5042
                21 November 2018
                Nov-Dec 2018
                : 3
                : 6
                : e00597-18
                Affiliations
                [a ]Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
                Antimicrobial Development Specialists, LLC
                University of Arkansas for Medical Sciences
                University of Idaho
                NIAID/NIH
                Author notes
                Address correspondence to Patrick M. Schlievert, Patrick-Schlievert@ 123456uiowa.edu .

                Citation Schlievert PM, Kilgore SH, Kaus GM, Ho TD, Ellermeier CD. 2018. Glycerol monolaurate (GML) and a nonaqueous five-percent GML gel kill Bacillus and Clostridium spores. mSphere 3:e00597-18. https://doi.org/10.1128/mSphereDirect.00597-18.

                Article
                mSphere00597-18
                10.1128/mSphereDirect.00597-18
                6249644
                30463926
                6e87b5a8-35c0-473a-b62b-09d6c4b3b040
                Copyright © 2018 Schlievert et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 4 November 2018
                : 6 November 2018
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 30, Pages: 9, Words: 5240
                Funding
                Funded by: HHS | U.S. Public Health Service (USPHS), https://doi.org/10.13039/100007197;
                Award ID: AI087834
                Award Recipient :
                Funded by: University of Iowa (UI), https://doi.org/10.13039/100008893;
                Award Recipient :
                Categories
                Research Article
                Therapeutics and Prevention
                Editor's Pick
                Custom metadata
                November/December 2018

                bacillus,clostridium,endospores,glycerol monolaurate
                bacillus, clostridium, endospores, glycerol monolaurate

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