Drug efflux systems are major factors in the failure of chemical disinfection regimes aimed at controlling the spread of infectious microorganisms. Bacterial drug efflux is mediated by active membrane transport proteins that are classically organised into one of five families or superfamilies.
Chlorhexidine is widely used as an antiseptic or disinfectant in both hospital and community settings. Transcriptomic analysis of the chlorhexidine shock response of the nosocomial pathogen Acinetobacter baumannii allowed us to identify a novel chlorhexidine resistance determinant that we have named aceI. The AceI protein was purified and binding assays demonstrated direct and specific interactions between AceI and chlorhexidine. Transport assays using [14C]-chlorhexidine determined that AceI was able to mediate the energy-dependent efflux of chlorhexidine. Thus, AceI is an active chlorhexidine efflux protein and the founding member of a new family of bacterial drug efflux transporters. Functional analyses of AceI orthologues has revealed that this family includes multidrug efflux pumps that can transport more than a single substrate.
The aceI gene is encoded adjacent to a divergently transcribed LysR family regulator, which we have named as AceR. aceI expression is not induced in aceR deletion strains and purified AceR protein binds to the aceI/aceR intergenic region. These data suggest that AceR is a positive regulator of aceI expression in the presence of chlorhexidine.