HOW BACTERIA BIND MORE STRONGLY UNDER MECHANICAL FORCE: THE CATCH-BOND FIMH

摘要

We study a protein that responds to mechanical force in a most striking manner. We demonstrate that Escherichia coli bacteria need shear stress to bind to certain tissues and model surfaces; they bind strongest precisely when the body tries to wash them off. We have determined that the protein responsible for this behavior is FimH, a ubiquitous adhesion protein in intestinal bacteria that mediates adhesion to host cells via the carbohydrate mannose. Although mechanical force normally decreases bond lifetimes, we have shown that the bond between FimH and simple mono-mannose receptors is a "catch-bond" that lasts longer under shear stress. In contrast, structural variations in either FimH or the receptor cause a stronger mode of adhesion in static conditions with little or no activation under force. We derive a structural model for how mechanical force switches FimH to a strong binding mode by using steered molecular dynamics simulations, and validate the predictions with subsequent site-directed mutagenesis. The physiological consequences as well as the engineering principles suggested by the structural model will be discussed.