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Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion.


ABSTRACT: Clumping factor A (ClfA), a cell-wall-anchored protein from Staphylococcus aureus, is a virulence factor in various infections and facilitates the colonization of protein-coated biomaterials. ClfA promotes bacterial adhesion to the blood plasma protein fibrinogen (Fg) via molecular forces that have not been studied so far. A unique, yet poorly understood, feature of ClfA is its ability to favor adhesion to Fg at high shear stress. Unraveling the strength and dynamics of the ClfA-Fg interaction would help us better understand how S. aureus colonizes implanted devices and withstands physiological shear stress. By means of single-molecule experiments, we show that ClfA behaves as a force-sensitive molecular switch that potentiates staphylococcal adhesion under mechanical stress. The bond between ClfA and immobilized Fg is weak (?0.1 nN) at low tensile force, but is dramatically enhanced (?1.5 nN) by mechanical tension, as observed with catch bonds. Strong bonds, but not weak ones, are inhibited by a peptide mimicking the C-terminal segment of the Fg ?-chain. These results point to a model whereby ClfA interacts with Fg via two distinct binding sites, the adhesive function of which is regulated by mechanical tension. This force-activated mechanism is of biological significance because it explains at the molecular level the ability of ClfA to promote bacterial attachment under high physiological shear stress.

SUBMITTER: Herman-Bausier P 

PROVIDER: S-EPMC6003445 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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<i>Staphylococcus aureus</i> clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion.

Herman-Bausier Philippe P   Labate Cristina C   Towell Aisling M AM   Derclaye Sylvie S   Geoghegan Joan A JA   Dufrêne Yves F YF  

Proceedings of the National Academy of Sciences of the United States of America 20180507 21


Clumping factor A (ClfA), a cell-wall-anchored protein from <i>Staphylococcus aureus</i>, is a virulence factor in various infections and facilitates the colonization of protein-coated biomaterials. ClfA promotes bacterial adhesion to the blood plasma protein fibrinogen (Fg) via molecular forces that have not been studied so far. A unique, yet poorly understood, feature of ClfA is its ability to favor adhesion to Fg at high shear stress. Unraveling the strength and dynamics of the ClfA-Fg intera  ...[more]

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