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• W2118436958 startingPage "4139" @default.
• W2118436958 abstract "Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized in vitro serial passage experiments to derive C. difficile strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in C. difficile and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in C. difficile REA type BI, and a PadR family transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against C. difficile, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci." @default.
• W2118436958 created "2016-06-24" @default.
• W2118436958 creator A5025830085 @default.
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• W2118436958 creator A5058417247 @default.
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• W2118436958 creator A5084319285 @default.
• W2118436958 date "2015-07-01" @default.
• W2118436958 modified "2023-09-28" @default.
• W2118436958 title "Mutations Associated with Reduced Surotomycin Susceptibility in Clostridium difficile and Enterococcus Species" @default.
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• W2118436958 doi "https://doi.org/10.1128/aac.00526-15" @default.
• W2118436958 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4468737" @default.
• W2118436958 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25941217" @default.
• W2118436958 hasPublicationYear "2015" @default.
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