Bacterial adhesion to target cells enhanced by shear force

Area of Science:

• Microbiology
• Biophysics
• Molecular Biology

Background:

• Bacterial surface adhesion is crucial for infection and often occurs under shear stress.
• External forces are generally expected to weaken receptor-ligand interactions, reducing adhesion.
• The adhesin FimH in Escherichia coli plays a key role in bacterial attachment to host cells.

Purpose of the Study:

• To investigate the effect of shear stress on bacterial adhesion mediated by FimH.
• To elucidate the molecular mechanism behind shear-enhanced bacterial attachment.
• To determine if FimH functions as a force-sensitive molecule.

Main Methods:

• Flow chamber experiments using Escherichia coli and guinea pig erythrocytes.
• Steered molecular dynamics simulations of the FimH receptor binding domain.
• Site-directed mutagenesis to study FimH-receptor interactions.

Main Results:

• Bacterial attachment transitioned from loose to firm with a 10-fold increase in shear stress.
• Simulations revealed mechanical force extends the interdomain linker chain of FimH.
• Mutagenesis studies confirmed the role of linker extension in force-dependent binding.

Conclusions:

• FimH acts as a force sensor, enhancing bacterial adhesion under shear stress.
• The extension of the FimH interdomain linker is the molecular basis for this force-sensing capability.
• This mechanism allows bacteria to discriminate between surface-bound and soluble receptors.