Tetrathionate sensing enables Vibrio parahaemolyticus to repress quorum sensing for intestinal colonization

Quorum sensing (QS) enables bacterial coordination of group behaviors, yet how enteric pathogens modulate QS during intestinal colonization remains poorly understood. Here, we demonstrated that Vibrio parahaemolyticus represses QS to promote gut colonization through sensing of self‑generated tetrathionate derived from host thiosulfate. We found that the cecal extracts from healthy mouse contained thiosulfate, which could be converted to tetrathionate by V. parahaemolyticus via the thiosulfate dehydrogenase TsdBA. The two‑component system TtrRS then sensed this self‑produced tetrathionate and, via the global silencer H‑NS, repressed expression of the master QS regulator OpaR independently of the canonical QS receptors. Transcriptomic analyzes initially uncovered a cross‑talk between TtrRS and OpaR, showing co‑regulation of 76 genes with opposing patterns, and further study demonstrated that OpaR directly binds and represses the tsdBA promoter, establishing a coherent regulatory loop in which TtrRS and OpaR converge on shared target genes. Deletion of opaR significantly enhanced bacterial colonization in a mouse model, indicating that QS actively restricts intestinal fitness of V. parahaemolyticus, a restriction that is relieved by TtrRS‑mediated QS repression. Collectively, V. parahaemolyticus exploits TsdBA‑dependent tetrathionate generation to downregulate QS through a TtrRS-H-NS-OpaR cascade, with cross‑talk between TtrRS and OpaR fine‑tuning this adaptive response, thereby conferring a competitive advantage in the host gut. These findings provide a new model for how enteric pathogens integrate sulfur metabolism and QS repression to optimize host colonization.