Medicine and Health Sciences
Vibrio cholerae colonization of the host requires stringent response activation of TCP, the Toxin-Coregulated Pilus
Cholera is an epidemic diarrheal disease caused by the Gramnegative bacterium Vibrio cholerae. In order to colonize a host, V. cholerae must express the toxin-coregulated pilus (TCP), and diarrheal symptoms are primarily produced by the virulence factor cholera toxin (CT). CT and TCP expression is regulated by the ToxR regulon. Components of the ToxR regulon include ToxT, a transcription factor that directly initiates transcription of the CT and TCP genes. Upstream regulators include the integral membrane proteins TcpP and ToxR, transcription factors necessary for expression of toxT. ToxR may also directly initiate transcription of the CT genes independently of ToxT. It is thought that TCP is required early in infection to colonize the small intestine and that CT is expressed later in order to produce diarrhea and escape the host. We found that stringent response, the universally-conserved low nutrient stress response, was necessary for colonization of the mouse small intestine. The hypothesis tested was that bacterial evaluation of nutrient environment regulated virulence genes through the stringent response control of the ToxR regulon. Deletions in the stringent response genes and of the ToxR regulon genes were made and these mutants used to determine where stringent response fit into the virulence gene regulatory system. Stringent response activated gene expression of virulence factors (those encoding CT and TCP) and some ToxR regulon components (toxT and tcpP) while it repressed others (toxR). The gene expression data was consistent with the requirement for stringent response-dependent colonization of the mouse; stringent response was required for TCP expression, with TCP required for colonization. The gene expression data showing that stringent response had differential effects on components in the ToxR regulon may explain how CT and TCP may be differentially regulated in infection despite being controlled by the same transcriptional activators.
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Raskin, David; Mishra, Arunima; He, Huajun; Mall, Swathi; and Cooper, Jennifer, "Stringent Response Regulation of Virulence Factors in Vibrio Cholera" (2016). MU-COM Research Day. 20.