LysR family activator-regulated major facilitator superfamily transporters are involved in Vibrio cholerae antimicrobial compound resistance and intestinal colonisation

Expression of a multidrug resistance transporter renders bacterial cells resistant to a variety of drugs. The major facilitator superfamily (MFS) comprises the largest group of bacterial multidrug transporters. There are over 20 MFS efflux pumps annotated on the genome of Vibrio cholerae, but little is known about their functions and regulation. In this study, five MFS efflux pumps were characterised, each of which is associated with a divergently transcribed putative LysR-type transcriptional regulator (MfsR). It was found that each of these MFS structural genes is regulated by the corresponding MfsR regulator. Deletion of these five mfs genes results in increased susceptibility to tetracycline and crude bile as well as a colonisation defect in an infant mouse colonisation model. Moreover, tetracycline and unknown intestinal signals could serve as co-inducers for the MfsR regulators. These data suggest that MFS efflux pumps are important both for antimicrobial resistance and V. cholerae pathogenesis.