Vibrio cholerae virulence activator ToxR regulates manganese transport and resistance of reactive oxygen species.

Like many other pathogens, Vibrio cholerae, the causative agent of cholera, can modulate its gene expression to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). We previously reported that the virulence activator AphB in V. cholerae is involved in ROS resistance. In this study, we found that another key virulence regulator, ToxR, was important for V. cholerae resistance to hydrogen peroxide. Through a genome-wide transposon screen, we discovered that a deletion in mneA, which encodes a manganese exporter, restored ROS resistance of the toxR mutant. We then showed that ToxR did not affect mneA transcription, but the ToxR-regulated major porin OmpU is critical for ROS resistance. Addition of manganese in culture media restored ROS resistance in both toxR and ompU mutants. Furthermore, elemental analysis indicated that the intracellular concentration of manganese in both toxR and ompU mutants was reduced. This may result in intracellular ROS accumulation in these mutants. Our data suggest that ToxR plays an important role in the resistance of reactive oxygen species through the regulation of manganese transport.