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

Research output: Contribution to journalArticle

Authors

  • Philippe Herman-Bausier
  • Cristina Labate
  • Aisling M Towell
  • Sylvie Derclaye
  • Yves F Dufrêne

Colleges, School and Institutes

External organisations

  • JMP Life Sciences, SAS Institute
  • Trinity College Dublin
  • Walloon Excellence in Life Sciences and Biotechnology

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 γ-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.

Bibliographic note

Copyright © 2018 the Author(s). Published by PNAS.

Details

Original languageEnglish
Pages (from-to)5564-5569
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number21
Early online date7 May 2018
Publication statusPublished - 22 May 2018

Keywords

  • Bacterial Adhesion/physiology, Binding Sites, Biomechanical Phenomena, Cells, Cultured, Coagulase/genetics, Fibrinogen/genetics, Molecular Dynamics Simulation, Protein Binding, Staphylococcal Infections/microbiology, Staphylococcus aureus/physiology