Vibrio cholerae OmpU and OmpT porins are differentially affected by bile.

OmpT and OmpU are pore-forming proteins of the outer membrane of Vibrio cholerae, a pathogen that colonizes the intestine and produces cholera. Expression of the ompU and ompT genes is under the regulation of ToxR, a transmembrane transcriptional activator that also controls expression of virulence factors. It was recently shown that bile stimulates the ToxR-mediated transcription of ompU and that ompU-expressing strains are more resistant to bile and anionic detergents than ompT-expressing cells. In order to further understand the role of the OmpT and OmpU porins in the ability of V. cholerae to survive and colonize the host intestine, we examined the outer membrane permeability of cells expressing only ompU or only ompT or both genes in the absence and in the presence of bile. By comparing various strains in terms of the rate of degradation of the beta-lactam antibiotic cephaloridine by the periplasmic beta-lactamase, we found that the permeation of the antibiotic through the outer membrane of OmpU-containing cells was slower than the permeation in OmpT-containing cells. In addition, the OmpU-mediated outer membrane permeability was not affected by external bile, while the OmpT-mediated antibiotic flux was reduced by bile in a concentration-dependent manner. Our results confirm that OmpT and OmpU provide a passageway for hydrophilic solutes through the outer membrane and demonstrate that bile might interfere with this traffic in OmpT-producing cells by functionally inhibiting the OmpT pore. The insensitivity of OmpU to bile may be due to its small pore size and may provide an explanation for the resistance of OmpU-producing cells to bile in vivo.