Virulence response of escherichia coli O157:H7 to bile salts and short chain fatty acids

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a gastrointestinal pathogen which causes hemorrhagic colitis and can lead to neurological damage, acute kidney failure (hemolytic uremic syndrome and vascular lesions. During intestinal colonization EHEC is exposed to a variety of stresses including bile salts (BS) in the small intestine and short chain fatty acids (SCFA) in the large intestine; little is known about how these stresses affect this pathogen's virulence properties. The goal of this study was to investigate the impact of exposure of E. coli O157:H7 to physiologically relevant concentrations of BS and SCFA alone and in mixtures on bacterial survival, verotoxin production and adhesion to human epithelial cells. The results indicated that BS treatments significantly enhanced several virulence properties including survival and adhesion to human epthelial cell lines including colonic epithelial cells. Verotoxin production was not affected by any of the BS treatments. Bacterial pretreatment with erythromycin at a sub-minimal inhibitory concentration eliminated the adhesion enhancement after BS treatment, suggesting that protein synthesis was required for enhanced adhesion of BS treated organisms. Using the isogenci mutant of the known adhesions, intimin and iha it was established that there was no role for intimin or iha in the BS-induced adhesion enhancement. SCFA treatments reduced bacterial viability but significantly enhanced both adhesion to human epithelial cells and verotoxin production. The results of this research indicate that ingestion stresses such as BS and SCFA, which are part of the host's natural chemical assault on foreign organisms, may actually enhance the viulence properties of this pathogen and contribute to, rather than, prevent infection. Furthermore, they suggest that this pathogen may use these ingestion stresses to cue the expression of numerous virulence factors for successful infection of local microenvironments.