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            <title xml:lang="en">The role of the CroR response regulator in resistance of Enterococcus faecalis to D-cycloserine is defined using an inducible receiver domain</title>
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                <forename type="first">Cécile</forename>
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                <title xml:lang="en">The role of the CroR response regulator in resistance of Enterococcus faecalis to D-cycloserine is defined using an inducible receiver domain</title>
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                <title level="j">Molecular Microbiology</title>
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              <p>Enterococcus faecalisis an opportunistic multidrug-resistant human pathogen causing severe nosoco-mial infections. Previous investigations revealed thatthe CroRS two-component regulatory pathway likelydisplays a pleiotropic role inE. faecalis, involved invirulence,  macrophage  survival,  oxidative  stressresponse as well as antibiotic resistance. Therefore,CroRS represents an attractive potential new targetfor antibiotherapy. In this report, we further exploredCroRS cellular functions by characterizing the CroRregulon: the ‘domain swapping’ method was appliedand a CroR chimera protein was generated by fusingthe receiver domain from NisR to the output domainfrom CroR. After demonstrating that the chimeraCroR complements acroRgene deletion inE. faeca-lis(stress response, virulence), we conducted aglobal gene expression analysis using RNA-Seq andidentified 50 potential CroR targets involved in multi-ple cellular functions such as cell envelope homeo-stasis, substrate transport, cell metabolism, geneexpression regulation, stress response, virulenceand antibiotic resistance. For validation, CroR directbinding to several candidate targets was demon-strated by EMSA. Further, this work identifiedalr, thegene  encoding  the  alanine  racemase  enzymeinvolved inE. faecalisresistance to D-cycloserine, apromising antimicrobial drug to treat enterococcalinfections, as a member of the CroR regulon.</p>
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