FimH-mannose noncovalent bonds survive minutes to hours under force.

The adhesin FimH is expressed by commensal Escherichia coli and is implicated in urinary tract infections, where it mediates adhesion to mannosylated glycoproteins on urinary and intestinal epithelial cells in the presence of a high-shear fluid environment. The FimH-mannose bond exhibits catch behavior in which bond lifetime increases with force, because tensile force induces a transition in FimH from a compact native to an elongated activated conformation with a higher affinity to mannose. However, the lifetime of the activated state of FimH has not been measured under force. Here we apply multiplexed magnetic tweezers to apply a preload force to activate FimH bonds with yeast mannan, then we measure the lifetime of these activated bonds under a wide range of forces above and below the preload force. A higher fraction of FimH-mannan bonds were activated above than below a critical preload force, confirming the FimH catch bond behavior. Once activated, FimH detached from mannose with multi-state kinetics, suggesting the existence of two bound states with a 20-fold difference in dissociation rates. The average lifetime of activated FimH-mannose bonds was 1000 to 10,000 s at forces of 30-70 pN. Structural explanations of the two bound states and the high force resistance provide insights into structural mechanisms for long-lived, force-resistant biomolecular interactions.