The virulence regulator ToxT influences Vibrio cholerae motility through the expression of the methyl-accepting chemoreceptors AcfB and TcpI

Abstract

ABSTRACT Vibrio cholerae is the causative agent of the human diarrheal disease cholera. Previous studies identified “hyperswarming” (HS) mutant V. cholerae with enhanced motility and decreased virulence factor expression, but the genetic basis of HS was unknown. Through whole-genome sequencing, we have identified point mutations within toxT , which encodes the master virulence regulator, as being responsible for the HS phenotype. These mutations are loss of function, and they eliminate transcription of cholera toxin and toxin-coregulated pilus genes. Using single-cell video tracking, these HS strains were also observed to exhibit enhanced motility/chemotaxis (increased speed and decreased directional change). Two methyl-accepting chemoreceptors (methyl-accepting chemotaxis proteins), AcfB and TcpI, are positively regulated by ToxT, and expression of both AcfB and TcpI within HS mutants restores wild-type motility. Moreover, a V. cholerae strain with a hyperactive ToxT (N106A) exhibits reduced motility (decreased speed and increased directional change), and knocking out acfB and tcpI in this strain restores wild-type motility. AcfB and TcpI localize to the bacterial cell poles, suggesting they incorporate into the chemotaxis arrays to modulate swimming behavior. Our findings demonstrate that the absence of the ToxT-dependent MCPs AcfB and TcpI is responsible for the HS phenotype, demonstrating a direct role of ToxT in the swimming behavior of V. cholerae . IMPORTANCE Vibrio cholerae causes the human diarrheal disease cholera, and the master virulence regulator ToxT is responsible for the expression of the most important virulence factors, cholera toxin and the toxin-coregulated pilus, necessary for disease. Motility is also important for the bacteria to cause disease, and in this study, we provide evidence that ToxT also modulates motility, providing a regulatory link between motility and the other virulence factors required for the pathogenic lifestyle of V. cholerae .

The authors' abstract, as published at the source. Journal of Bacteriology, 2026 · DOI ↗