Modulators of Enterococcus Faecalis Cell Envelope Integrity and Antimicrobial Resistance Influence Stable Colonization of the Mammalian Gastrointestinal Tract

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dc.contributor.ORCID0000-0002-7343-9271 (Palmer, KL)en_US
dc.contributor.authorBanla, Ismael L.en_US
dc.contributor.authorKommineni, Sushmaen_US
dc.contributor.authorHayward, Michaelen_US
dc.contributor.authorRodrigues, Marinelleen_US
dc.contributor.authorPalmer, Kelli L.en_US
dc.contributor.authorSalzman, Nita H.en_US
dc.contributor.authorKristich, Christopher J.en_US
dc.contributor.utdAuthorRodrigues, Marinelleen_US
dc.contributor.utdAuthorPalmer, Kelli L.en_US
dc.date.accessioned2018-10-22T19:36:47Z
dc.date.available2018-10-22T19:36:47Z
dc.date.created2017-10-16en_US
dc.date.issued2018-10-22
dc.descriptionFull text access from Treasures at UT Dallas is restricted to current UTD affiliates.en_US
dc.description.abstractThe Gram-positive bacterium Enterococcus faecalis is both a colonizer of the gastrointestinal tract (GIT) and an agent of serious nosocomial infections. Although it is typically required for pathogenesis, GIT colonization by E. faecalis is poorly understood. E. faecalis tolerates high concentrations of GIT antimicrobials, like cholate and lysozyme, leading us to hypothesize that resistance to intestinal antimicrobials is essential for long-term GIT colonization. Analyses of E. faecalis mutants exhibiting defects in antimicrobial resistance revealed that IreK, a determinant of envelope integrity and antimicrobial resistance, is required for long-term GIT colonization. IreK is a member of the PASTA kinase protein family, bacterial transmembrane signaling proteins implicated in the regulation of cell wall homeostasis. Among several determinants of cholate and lysozyme resistance in E. faecalis, IreK was the only one found to be required for intestinal colonization, emphasizing the importance of this protein to enterococcal adaptation to the GIT. By studying.ireK suppressor mutants that recovered the ability to colonize the GIT, we identified two conserved enterococcal proteins (OG1RF_11271 and OG1RF_11272) that function antagonistically to IreK and interfere with cell envelope integrity, antimicrobial resistance, and GIT colonization. Our data suggest that IreK, through its kinase activity, inhibits the actions of these proteins. IreK, OG1RF_11271, and OG1RF_11272 are found in all enterococci, suggesting that their effect on GIT colonization is universal across enterococci. Thus, we have defined conserved genes in the enterococcal core genome that influence GIT colonization through their effect on enterococcal envelope integrity and antimicrobial resistance.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorship"This study was supported by grant R01 AI081692 and OD006447 from the National Institutes of Health (NIH) to C.J.K. and grant R01 AI116610 to K.L.P., as well as grant R01 GM099526 to N.H.S.; American Heart Association Midwest Affiliate Predoctoral Fellowship 16PRE29700011 to I.L.B."en_US
dc.identifier.bibliographicCitationBanla, Ismael L., Sushma Kommineni, Michael Hayward, Marinelle Rodrigues, et al. 2018. "Modulators of enterococcus faecalis cell envelope integrity and antimicrobial resistance influence stable colonization of the mammalian gastrointestinal tract." Infection and Immunity 2018(86), doi:10.1128/IAI.00381-17en_US
dc.identifier.issn0019-9567en_US
dc.identifier.issue86en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6224
dc.language.isoenen_US
dc.publisherAmer Soc Microbiologyen_US
dc.relation.urihttp://dx.doi.org/10.1128/IAI.00381-17
dc.rights©2017 American Society for Microbiology. All Rights Reserved.en_US
dc.sourceInfection and Immunity
dc.subjectEnterococcus faecalisen_US
dc.subjectAmino acid sequenceen_US
dc.subjectBacillus subtilisen_US
dc.subjectIntestinesen_US
dc.subjectStaphylococcus aureusen_US
dc.subjectImmunologyen_US
dc.subjectCommunicable Diseasesen_US
dc.subjectAnti-Infective Agentsen_US
dc.titleModulators of Enterococcus Faecalis Cell Envelope Integrity and Antimicrobial Resistance Influence Stable Colonization of the Mammalian Gastrointestinal Tracten_US
dc.type.genrearticleen_US

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