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

Binding\nof Staphylococcus aureus surface proteins\nto endothelial cell integrins plays essential roles\nin host cell adhesion and invasion, eventually leading to life-threatening\ndiseases. The staphylococcal protein IsdB binds to β3-containing\nintegrins through a mechanism that has never been thoroughly investigated.\nHere, we identify and characterize at the nanoscale a previously undescribed\nstress-dependent adhesion between IsdB and integrin α_Vβ₃. The strength of single IsdB−α_Vβ₃ interactions is moderate (∼100\npN) under low stress, but it increases dramatically under high stress\n(∼1000–2000 pN) to exceed the forces traditionally reported\nfor the binding between integrins and Arg-Gly-Asp (RGD) sequences.\nWe suggest a mechanism where high mechanical stress induces conformational\nchanges in the integrin from a low-affinity, weak binding state to\na high-affinity, strong binding state. This single-molecule study\nhighlights that direct adhesin–integrin interactions represent\npotential targets to fight staphylococcal infections.