Enterotoxigenic Escherichia coli promotes its adherence to intestinal epithelial cells through heat-labile enterotoxin-dependent and independent mechanisms

Enterotoxigenic Escherichia coli (ETEC) is the most common etiology of travelers' diarrhea and a major endemic health threat in developing nations. While human infection with ETEC is relatively uncommon in industrialized countries, infection of pigs with host-specific porcine ETEC causes post-weaning diarrhea that is a significant burden to the pork industry. Despite the global prevalence and importance of these enteric pathogens, the full complement of virulence determinants responsible for intestinal colonization remains undetermined. Given recent evidence suggesting that the heat-labile enterotoxin (LT) provides a distinct colonization advantage for ETEC in vivo, we hypothesized that LT preconditions the host intestinal epithelium for ETEC adherence. To test this hypothesis, we used an in vitro model of ETEC adherence to examine more closely the role of LT in promoting bacterial-host interactions. Here we present data demonstrating that elaboration of LT promotes a significant increase in E. coli adherence. We also determined that increased adherence is dependent on the ADP-ribosylating activity of LT. Experiments are also presented that probe the ability of porcine ETEC isolates to induce apoptosis and cell death in porcine intestinal epithelial cells. Quantification of changes in host phosphatidylserine exposure following ETEC infection suggests that ETEC induce early stages of host apoptosis independent of LT. ETEC infection also causes a drastic inhibition of host esterase activity. We raise the possibility that ETEC may induce the early stages of host apoptosis to gain access to otherwise cryptic host receptors.