Molecular mechanism of shear-enhanced bacterial adhesion

How can bacteria colonize tissues that are regularly washed by body fluids? FimH is an adhesion protein found on Escherichia coli and many other bacteria that mediates adhesion to host cells via the carbohydrate mannose. We showed recently that E. coli has evolved a nanoscale adhesion switch that binds strongly to monomannose under elevated shear stress and weakly otherwise. Though shear force normally decreases bond lifetimes, shear-enhanced adhesion by FimH is mediated by a force-induced structural change in the adhesion that switches from low to high affinity if mechanically stretched. This is the first demonstration of a "catch-bond" that strengthens under mechanical force similar to a Chinese finger trap. We used steered molecular dynamics to derive a structural model how mechanical force activates the switch, and subsequent site-directed mutagenesis to validate the predictions. In contrast, E. coli binds more strongly to complex trimannose receptors in low shear, but this binding weakens under mechanical force as expected for a "slip bond". The structural model and the physiological consequences will be discussed.