ToxT Regulon Is Nonessential for Vibrio cholerae Colonization in Adult Mice.

Vibrio cholerae is the causative agent of cholera, a life-threatening diarrheal disease in humans. The ability of V. cholerae to colonize the intestine of different animals is a key factor for its fitness and transmissibility between hosts. Many virulence factors, including the ToxT regulon, have been identified to be the major components allowing V. cholerae to colonize the small intestine of suckling mice; however, the mechanism of V. cholerae colonization in the adult mammalian intestine is unclear. In this study, using the streptomycin-treated adult mouse animal model, we characterized the role of the ToxT regulon in V. cholerae colonization in adult mammalian intestine. We first found that the activity of TcpP regulating ToxT regulon expression was attenuated by intestinal reactive oxygen species (ROS). We then found that V. cholerae containing a deletion of the ToxT regulon showed a competition advantage in colonizing adult mice; however, a mutant containing a constitutively active ToxT regulon showed a significant defect in colonizing adult mice. Constitutively producing the virulence factors in the ToxT regulon causes a V. cholerae competition defect in nutrient-limiting conditions. The results of this study demonstrate that modulating the activity of the ToxT regulon through ROS sensed by TcpP is critical for V. cholerae to enhance its colonization in the intestine of adult mice.