TY - JOUR TI - The giant staphylococcal protein Embp facilitates colonization of surfaces through Velcro-like attachment to fibrillated fibronectin AU - Khan, Nasar AU - Aslan, Hüsnü AU - Büttner, Henning AU - Rohde, Holger AU - Golbek, Thaddeus Wayne AU - Roeters, Steven Joop AU - Woutersen, Sander AU - Weidner, Tobias AU - Meyer, Rikke Louise A2 - Cooper, Vaughn S A2 - Garrett, Wendy S A2 - Fey, Paul VL - 11 PY - 2022 DA - 2022/07/07 SP - e76164 C1 - eLife 2022;11:e76164 DO - 10.7554/eLife.76164 UR - https://doi.org/10.7554/eLife.76164 AB - Staphylococcus epidermidis causes some of the most hard-to-treat clinical infections by forming biofilms: Multicellular communities of bacteria encased in a protective matrix, supporting immune evasion and tolerance against antibiotics. Biofilms occur most commonly on medical implants, and a key event in implant colonization is the robust adherence to the surface, facilitated by interactions between bacterial surface proteins and host matrix components. S. epidermidis is equipped with a giant adhesive protein, extracellular matrix-binding protein (Embp), which facilitates bacterial interactions with surface-deposited, but not soluble fibronectin. The structural basis behind this selective binding process has remained obscure. Using a suite of single-cell and single-molecule analysis techniques, we show that S. epidermidis is capable of such distinction because Embp binds specifically to fibrillated fibronectin on surfaces, while ignoring globular fibronectin in solution. S. epidermidis adherence is critically dependent on multivalent interactions involving 50 fibronectin-binding repeats of Embp. This unusual, Velcro-like interaction proved critical for colonization of surfaces under high flow, making this newly identified attachment mechanism particularly relevant for colonization of intravascular devices, such as prosthetic heart valves or vascular grafts. Other biofilm-forming pathogens, such as Staphylococcus aureus, express homologs of Embp and likely deploy the same mechanism for surface colonization. Our results may open for a novel direction in efforts to combat devastating, biofilm-associated infections, as the development of implant materials that steer the conformation of adsorbed proteins is a much more manageable task than avoiding protein adsorption altogether. KW - Staphylococcus epidermidis KW - Embp KW - fibronectin KW - bacterial adhesion KW - multivalent KW - AFM JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -