Pathoadaptive conditional regulation of the type VI secretion system in Vibrio cholerae O1 strains

Themost recently discovered secretion pathway in Gram-negative bacteria, the type VI secretion system (T6SS), is present in many species and is considered important for the survival of non-O1 non-O139 Vibrio cholerae in aquatic environments. Until now, it was not known whether there is a functionally active T6SS in wild-type V. choleraeO1 strains, the cause of cholera dis-ease in humans. Here, we demonstrate the presence of a functionally active T6SS in wild-type V. choleraeO1 strains, as evi-denced by the secretion of the T6SS substrate Hcp, which required several gene products encoded within the putative vas gene cluster. Our analyses showed that the T6SS of wild-type V. choleraeO1 strain A1552 was functionally activated when the bacteria were grown under high-osmolarity conditions. The T6SS was also active when the bacteria were grown under low temperature (23°C), suggesting that the systemmay be important for the survival of the bacterium in the environment. A test of the interbac-terial virulence of V. cholerae strain A1552 against an Escherichia coli K-12 strain showed that it was strongly enhanced under high osmolarity and that it depended on the hcp genes. Interestingly, we found that the newly recognized osmoregulatory pro-tein OscR plays a role in the regulation of T6SS gene expression and secretion of Hcp from V. choleraeO1 strains. The severe diarrheal disease cholera is caused by Vibrio choleraebacteria of serogroups O1 and O139 that carry the ctxAB and tcp genes, encoding cholera toxin and toxin-coregulated pili, re-spectively (22). These bacteria have been the cause of seven pan-demics since 1817 (12, 38, 42). Non-O1, non-O139 V. cholera