Single-Molecule Analysis Demonstrates Stress-Enhanced Binding between Staphylococcus aureus Surface Protein IsdB and Host Cell Integrins

Nano Lett. 2020 Dec 9;20(12):8919-8925. doi: 10.1021/acs.nanolett.0c04015. Epub 2020 Nov 25.


Binding of Staphylococcus aureus surface proteins to endothelial cell integrins plays essential roles in host cell adhesion and invasion, eventually leading to life-threatening diseases. The staphylococcal protein IsdB binds to β3-containing integrins through a mechanism that has never been thoroughly investigated. Here, we identify and characterize at the nanoscale a previously undescribed stress-dependent adhesion between IsdB and integrin αVβ3. The strength of single IsdB-αVβ3 interactions is moderate (∼100 pN) under low stress, but it increases dramatically under high stress (∼1000-2000 pN) to exceed the forces traditionally reported for the binding between integrins and Arg-Gly-Asp (RGD) sequences. We suggest a mechanism where high mechanical stress induces conformational changes in the integrin from a low-affinity, weak binding state to a high-affinity, strong binding state. This single-molecule study highlights that direct adhesin-integrin interactions represent potential targets to fight staphylococcal infections.

Keywords: IsdB; binding strength; catch bond; single-molecule; staphylococcal adhesion; αVβ3 integrins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / metabolism
  • Cation Transport Proteins
  • Humans
  • Membrane Proteins / metabolism
  • Protein Binding
  • Staphylococcal Infections*
  • Staphylococcus aureus*


  • Adhesins, Bacterial
  • Cation Transport Proteins
  • IsdB protein, Staphylococcus aureus
  • Membrane Proteins