The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins
Fig 5
Putative model for RND-mediated efflux in environmental sensing.
(A) In WT cells growing under virulence gene inducing conditions the RND transporters expel metabolites from within the periplasm and ToxR functions with TcpP to activate ToxR regulon expression. Metabolites which are produced in the cytoplasm enter the periplasmic compartment either by passive diffusion through the cytoplasmic membrane or by active transport systems localized in the cytoplasmic membrane (denoted by the blue box). Exogenous metabolites enter the periplasm by diffusion through porin channels. (B) Inhibition of RND-mediated efflux results in the accumulation of metabolites that are normally expelled by the RND transporters. The accumulated metabolites activate ToxR via interaction with its periplasmic domain. Activated ToxR then modulates target gene expression (e.g. leuO) which leads to virulence repression and altered cell physiology. The accumulated metabolites also activate select two-component regulatory systems (e.g. CpxRA, CarRS, OmpREnvZ and VieSAB) which further effect transcriptional responses and environmental adaptation. Abbreviations: CT, cholera toxin; OM, outer membrane; PPD, periplasmic domain, RR, response regulator, TCP, toxin coregulated pilus; T, metabolite transporter.