Catch Bond-Mediated Adhesion Drives Staphylococcus aureus Host Cell Invasion

Various viruses and pathogenic bacteria interact withannexin A2to invade mammalian cells. Here, we show that Staphylococcusaureus engages in extremely strong catch bonds forhost cell invasion. By means of single-molecule atomic force microscopy,we find that bacterial surface-located clumping factors bind annexinA2 with extraordinary strength, indicating that these bonds are extremelyresilient to mechanical tension. By determining the lifetimes of thecomplexes under increasing mechanical stress, we demonstrate thatthe adhesins form catch bonds with their ligand that are capable tosustain forces of 1500-1700 pN. The force-dependent adhesionmechanism identified here provides a molecular framework to explainhow S. aureus pathogens tightly attachto host cells during invasion and shows promise for the design ofnew therapeutics against intracellular S. aureus.