Shear-enhanced binding of intestinal colonization factor antigen I of enterotoxigenic Escherichia coli.

摘要: In the intestine, enterotoxigenic Escherichia coli works against peristaltic forces, adhering to epithelium via colonization factor antigen I (CFA/I) fimbrial adhesin CfaE. The CfaE is similar in localization and tertiary (but not primary) structure FimH, type 1 of uropathogenic E. coli, which shows shear-dependent binding epithelial receptors by an allosteric catch-bond mechanism. Thus, we speculated that also capable shear-enhanced binding. Indeed, bovine erythrocytes coursing over immobilized CFA/I fimbriae flow chambers exhibited low accumulation levels fast rolling at shear, but 80-fold increase threefold decrease velocity elevated shear. This effect was reversible abolished pre-incubation with anti-CfaE antibody. Erythrocytes bound whole same manner, domain a shear-inhibitable fashion. Residue replacements designed disrupt interdomain interaction decreased shear dependency adhesion increased under static conditions human intestinal cells. These findings indicate close between adhesive anchoring pilin domains keeps former low-affinity state toggles into high-affinity upon separation two domains, all consistent mechanism