CexE Is A Virulence Factor ofCitrobacter rodentiumAnd Present In Enteric Pathogens Of Humans

Abstract

AbstractCexE is a 12 kDa protein that was originally reported to be present in just three strains of enterotoxigenicEscherichia 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 enteroaggregativeE. coli(EAEC) and other enteric pathogens includingYersinia enterocolitica, Providencia alcalifaciens, andCitrobacter rodentium. CexE and its homologs are expressed within virulence regulons of ETEC, EAEC, andC. 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 testedin 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 adherencein vitro, it does facilitate colonization of murine intestinal tissues byC. rodentium in vivo. In adult mice wild-type bacteria reached significantly higher loads and were shed in higher numbers than acexE::kanmutant. 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 thecexE::kanstrain 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.