Single-Molecule Analysis Demonstrates Stress-Enhanced Binding between <i>Staphylococcus aureus</i> Surface Protein IsdB and Host Cell Integrins.

Mathelié-Guinlet, Marion; Viela, Felipe; Alfeo, Mariangela Jessica; Pietrocola, Giampiero; Speziale, Pietro; Dufrêne, Yves F · Nano Lett · 2020

basic_science · Level V

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Abstract

Binding of <i>Staphylococcus aureus</i> 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 α<sub>V</sub>β<sub>3</sub>. The strength of single IsdB-α<sub>V</sub>β<sub>3</sub> 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.

Medical subject headings