A Giant Extracellular Matrix Binding Protein of <i>Staphylococcus epidermidis</i> Binds Surface-Immobilized Fibronectin via a Novel Mechanism
Henning Büttner, Markus Perbandt, Thomas P. Kohler, Alexey Kikhney, Manuel Wolters, Martin Christner, Marisol Heise, Jerome Pascal Wilde, Samira Weißelberg, Anna Both, Christian Betzel, Sven Hammerschmidt, Dmitri I. Svergun, Martin Aepfelbacher, Holger Rohde
Abstract
Staphylococcus epidermidis is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 β-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of S. epidermidis to surface-immobilized Fn.