Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices
Proceedings of the National Academy of Sciences
adhesion, binding strength, host-pathogen interaction, pacemaker, prosthesis
Bacterial Infections and Mycoses | Biophysics | Cell Biology | Microbial Physiology | Microbiology
Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a biofilm, a structured community of bacterial cells adherent to the surface of a solid substrate. Every biofilm begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated from humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct binding-force signature and had specific single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.
Lower, Steven K.; Lamlertthon, Supaporn; Casillas-Ituarte, Nadia N.; Lins, Roberto D.; Youngsunthon, Ruchirej; Taylor, Eric S.; DiBartola, Alex C.; Edmonson, Catherine; McIntyre, Lauren M.; Barth Reller, L; Que, Yok-Ai; Ros, Robert; Lower, Brian H.; and Fowler, Vance G. Jr. (2011). Polymorphisms in fibronectin binding protein A of Staphylococcus aureus are associated with infection of cardiovascular devices. Proceedings of the National Academy of Sciences 108(45), 18372-18377. doi: 10.1073/pnas.1109071108 Retrieved from https://digitalcommons.kent.edu/geolpubs/207