CexE Is A Virulence Factor of Citrobacter rodentium And Present In Enteric Pathogens Of Humans

Abstract

CexE is a 12 kDa protein that was originally reported to be present in just three strains of enterotoxigenic Escherichia coli (ETEC); a frequent causes of diarrheal illnesses worldwide. However, an examination of recently sequenced genomes has revealed that CexE is actually present in a majority of ETEC strains. Homologs of CexE are also present in enteroaggregative E. coli (EAEC) and other enteric pathogens including Yersinia enterocolitica, Providencia alcalifaciens, and Citrobacter rodentium. CexE and its homologs are expressed within virulence regulons of ETEC, EAEC, and C. rodentium. This, along with its distribution across several species of enteric pathogens, suggest that CexE confers a selective advantage to these pathogens. However, this hypothesis has yet to be tested in vivo. Here we demonstrate that CexE is conditionally secreted to the external leaf of the outer membrane of ETEC. Although CexE does not appear to play a role in adherence in vitro, it does facilitate colonization of murine intestinal tissues by C. rodentium in vivo. In adult mice wild-type bacteria reached significantly higher loads and were shed in higher numbers than a cexE::kan mutant. A similar trend was observed in neonatal mice. In addition, all of the neonates infected with the wild-type strain succumbed to infection within 16 days of inoculation. In contrast, 45% of the neonates infected with the cexE::kan strain survived for the 30 day duration of the experiment. These finding indicate that CexE is a conditionally secreted virulence factor that increases the colonization of hosts by enteric pathogens.