The two-component system TtrRS boosts Vibrio parahaemolyticus colonization by exploiting sulfur compounds in host gut.

One of the greatest challenges encountered by enteric pathogens is responding to rapid changes of nutrient availability in host. However, the mechanisms by which pathogens sense gastrointestinal signals and exploit available host nutrients for proliferation remain largely unknown. Here, we identified a two-component system in Vibrio parahaemolyticus, TtrRS, which senses environmental tetrathionate and subsequently activates the transcription of the ttrRS-ttrBCA-tsdBA gene cluster to promote V. parahaemolyticus colonization of adult mice. We demonstrated that TsdBA confers the ability of thiosulfate oxidation to produce tetrathionate which is sensed by TtrRS. TtrRS autoregulates and directly activates the transcription of the ttrBCA and tsdBA gene clusters. Activated TtrBCA promotes bacterial growth under micro-aerobic conditions by inducing the reduction of both tetrathionate and thiosulfate. TtrBCA and TsdBA activation by TtrRS is important for V. parahaemolyticus to colonize adult mice. Therefore, TtrRS and their target genes constitute a tetrathionate-responsive genetic circuit to exploit the host available sulfur compounds, which further contributes to the intestinal colonization of V. parahaemolyticus. Author summary: Access to host nutrients is regarded as a critical step for the pathogen infection. However, the human gastrointestinal tract is colonized by an enormous number of microbes, which limits pathogens' access to nutrient supplies. Sulfur is one of the most abundant elements on Earth and is also essential to all living organisms. The mechanisms by which bacteria, especially intestinal pathogens, regulate the bioavailability of utilizable sulfur in the host are poorly understood. Here, we characterized a tetrathionate-responsive genetic circuit, which was involved in the utilization of sulfur compounds including tetrathionate and thiosulfate in V. parahaemolyticus, and thus contributed to the bacterial intestinal colonization. Our study provides new insight into the ability of bacterial pathogens to sense gastrointestinal signals and exploit host nutrients for their colonization, which contributes to a better understanding of the pathogenesis of enteric pathogens. [ABSTRACT FROM AUTHOR]