Abstract
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.