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Two-component signal transduction systems (TCS) are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK) and a response regulator (RR). The  Vibrio cholerae  genome encodes 52 RR, but the role of these RRs in  V .  cholerae  pathogenesis is largely unknown. To identify RRs that control  V .  cholerae  colonization, in-frame deletions of each RR were generated and the resulting mutants analyzed using an infant mouse intestine colonization assay. We found that 12 of the 52 RR were involved in intestinal colonization. Mutants lacking one previously uncharacterized RR, VCA0566 (renamed VxrB), displayed a significant colonization defect. Further experiments showed that VxrB phosphorylation state on the predicted conserved aspartate contributes to intestine colonization. The VxrB regulon was determined using whole genome expression analysis. It consists of several genes, including those genes that create the type VI secretion system (T6SS). We determined that VxrB is required for T6SS expression using several in vitro assays and bacterial killing assays, and furthermore that the T6SS is required for intestinal colonization.  vxrB  is encoded in a four gene operon and the other  vxr  operon members also modulate intestinal colonization. Lastly, though Δ vxrB  exhibited a defect in single-strain intestinal colonization, the Δ vxrB  strain did not show any  in vitro  growth defect. Overall, our work revealed that a small set of RRs is required for intestinal colonization and one of these regulators, VxrB affects colonization at least in part through its regulation of T6SS genes.

Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System