Mutations Associated with Reduced Surotomycin Susceptibility in Clostridium Difficile and Enterococcus Species

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dc.contributor.authorAdams, Hannah M.en_US
dc.contributor.authorLi, X.en_US
dc.contributor.authorMascio, C.en_US
dc.contributor.authorChesnel, Laurenten_US
dc.contributor.authorPalmer, Kelli L.en_US
dc.contributor.utdAuthorAdams, Hannah M.en_US
dc.contributor.utdAuthorLi, X. Chesnel, Laurenten_US
dc.contributor.utdAuthorPalmer, Kelli L.en_US
dc.date.accessioned2017-04-25T19:33:37Z
dc.date.available2017-04-25T19:33:37Z
dc.date.created2015-05-04en_US
dc.date.issued2015-05-04en_US
dc.descriptionIncludes supplementary material.en_US
dc.description.abstractClostridium 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 endonu-clease 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.en_US
dc.identifier.bibliographicCitationAdams, H. M., X. Li, C. Mascio, L. Chesnel, et al. 2015. "Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species." Antimicrobial Agents and Chemotherapy 59(7), doi: 10.1128/AAC.00526-15en_US
dc.identifier.issn0066-4804en_US
dc.identifier.issue7en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5377
dc.identifier.volume59en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.urihttp://dx.doi.org/10.1128/AAC.00526-15
dc.rights©2015 American Society for Microbiology. All rights reserved.en_US
dc.sourceAntimicrobial Agents and Chemotherapy
dc.subjectAmoxicillinen_US
dc.subjectAmpicillinen_US
dc.subjectBacitracinen_US
dc.subjectCardiolipin synthaseen_US
dc.subjectCefalothinen_US
dc.subjectDaptomycinen_US
dc.subjectMetronidazoleen_US
dc.subjectRifampinen_US
dc.subjectCB-183,315 (surotomycin)en_US
dc.subjectLigasesen_US
dc.subjectVancomycinen_US
dc.subjectAmino Acid Sequenceen_US
dc.subjectAmino Acid Substitutionen_US
dc.subjectAnti-Bacterial Agentsen_US
dc.subjectBacillus subtilisen_US
dc.subjectMicrobial mutationen_US
dc.subjectEnterococcus faecalisen_US
dc.subjectEnterococcus faeciumen_US
dc.subjectFrameshift Mutationen_US
dc.subjectGene Expressionen_US
dc.subjectMutagenesisen_US
dc.subjectLactobacillus plantarumen_US
dc.subjectLipidsen_US
dc.subjectMicrobial Sensitivity Testsen_US
dc.subjectDrug Resistance, Multipleen_US
dc.subjectPhospholipidsen_US
dc.subjectGenetic Pleiotropyen_US
dc.subjectRestriction Mappingen_US
dc.subjectCodon, Terminatoren_US
dc.titleMutations Associated with Reduced Surotomycin Susceptibility in Clostridium Difficile and Enterococcus Speciesen_US
dc.type.genreArticleen_US

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