EfrEF and the Transcription Regulator ChlR Are Required for Chlorhexidine Stress Response in Enterococcus faecalis V583.

is an opportunistic pathogen and leading cause of health care-associated infections. Daily chlorhexidine gluconate (CHG) bathing of patients is generally regarded as an effective strategy to reduce the occurrence of health care-associated infections. It is likely that is frequently exposed to inhibitory and subinhibitory concentrations of CHG in clinical settings. The goal of this study was to investigate how the vancomycin-resistant strain V583 transcriptionally responds to and tolerates stress from CHG. We used transcriptome (microarray) analysis to identify genes upregulated by V583 in response to CHG. The genes (EF2226) and (EF2227), encoding a heterodimeric ABC transport system, were the most highly upregulated genes. expression was induced by CHG at concentrations several 2-fold dilutions below the MIC. Deletion of increased V583 susceptibility to CHG. We found that ChlR, a MerR-like regulator encoded by a sequence upstream of , mediated the CHG-dependent upregulation of , and deletion of also increased chlorhexidine susceptibility. Overall, our study gives insight into stress responses to a commonly used antiseptic.