TsrA Regulates Virulence and Intestinal Colonization in

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