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TsrA Regulates Virulence and Intestinal Colonization in Vibrio cholerae.


ABSTRACT: Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and ctxA, its broader function throughout the genome is unknown. Here, we find that deletion of tsrA results in genomewide expression patterns that heavily correlate with those seen upon deletion of hns, a widely conserved bacterial protein that regulates V. cholerae virulence. This correlation is particularly strong for loci on HAIs, where all differentially expressed loci in the ?tsrA mutant are also differentially expressed in the ?hns mutant. Correlation between TsrA and H-NS function extends to in vivo virulence phenotypes where deletion of tsrA compensates for the loss of ToxR activity in V. cholerae and promotes wild-type levels of mouse intestinal colonization. All in all, we find that TsrA broadly controls V. cholerae infectivity via repression of key HAI virulence genes and many other targets in the H-NS regulon.IMPORTANCE Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model.

SUBMITTER: DuPai CD 

PROVIDER: S-EPMC7729259 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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TsrA Regulates Virulence and Intestinal Colonization in <i>Vibrio cholerae</i>.

DuPai Cory D CD   Cunningham Ashley L AL   Conrado Aaron R AR   Wilke Claus O CO   Davies Bryan W BW  

mSphere 20201209 6


Pathogenic strains of <i>Vibrio cholerae</i> require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a <i>Vibrionaceae</i>-specific protein, is known to regulate the critical HAI virulence genes <i>toxT</i> and <i>ctxA</i>, its broader function throughout the genome is unknown. Here, we find that deletion of <i>tsrA</i> results in genomewide expression patterns that heavily correlate with those se  ...[more]

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