Acinetobacter baumannii is an increasingly problematic hospital-associated opportunistic human pathogen that causes a range of infections such as respiratory, urinary tract and blood infections. It has acquired a range of antibiotic resistance genes that have lead to the spread of multidrug resistant strains impervious to nearly all-available antibiotic treatments. The aim of this project is to directly study the regulation and activity of a recently identified AceI efflux system within the Proteobacterial antimicrobial compound efflux family (PACE), which can transport the biocide chlorhexidine and polyamines [1].
A LysR family regulator, AceR, is encoded adjacent to and divergently transcribed from the aceI gene. An Acinetobacter aceR mutant was susceptible to chlorhexidine, similar to an aceI deletion strain. AceI substrates (chlorhexidine and polyamines) are able to induce expression of AceI in wild-type Acinetobacter. However, aceI expression was not induced by substrate in the aceR deletion strain. Electropheretic gel mobility shift assays demonstrated that purified AceR protein was able to bind to the AceI/aceR intergenic region and biophysical assays showed that AceR can bind to AceI substrates. These results suggest AceR is a positive regulator of aceI gene expression. This study is important as AceR is the first regulator that was determined in the PACE family.