Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 21, Pages 5564-5569Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1718104115
Keywords
Staphylococcus aureus; ClfA; fibrinogen; shear stress; atomic force microscopy
Categories
Funding
- European Research Council under the European Union's Horizon Research and Innovation Programme [693630]
- Walloon Excellence in Life Sciences and Biotechnology [WELBIO-CR-2015A-05]
- National Fund for Scientific Research (FNRS)
- Research Department of the Communaute Francaise de Belgique (Concerted Research Action)
- European Research Council (ERC) [693630] Funding Source: European Research Council (ERC)
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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 (similar to 0.1 nN) at low tensile force, but is dramatically enhanced (similar to 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 gamma-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.
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