FimH-mannose noncovalent bonds survive minutes to hours under force

Area of Science:

• Biophysics
• Microbiology
• Structural Biology

Background:

• The adhesin FimH from Escherichia coli mediates bacterial adhesion to host cells.
• FimH exhibits catch bond behavior, where bond lifetime increases with applied force.
• The activated state's lifetime under force is critical for understanding FimH function but remains unmeasured.

Purpose of the Study:

• To measure the lifetime of activated FimH-mannose bonds under varying forces.
• To investigate the structural basis of FimH's force-resistant adhesion.
• To confirm FimH catch bond behavior by measuring activation dependence on preload force.

Main Methods:

• Multiplexed magnetic tweezers were used to apply preload forces and activate FimH-mannose bonds.
• The dissociation kinetics of activated FimH-mannose bonds were measured across a range of forces.
• Yeast mannan was used as the target ligand for FimH.

Main Results:

• A higher fraction of FimH bonds were activated above a critical preload force, confirming catch bond behavior.
• Activated FimH detached from mannose via multi-state kinetics, indicating at least two distinct bound states.
• The average lifetime of activated FimH-mannose bonds ranged from 1000 to 10,000 seconds at forces of 30-70 pN.

Conclusions:

• Activated FimH-mannose bonds exhibit exceptionally long lifetimes and high force resistance.
• The multi-state detachment kinetics suggest complex structural rearrangements within the FimH-mannose interaction.
• These findings provide structural insights into force-resistant biomolecular interactions, relevant to FimH-mediated infections.