The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus

• Published in: European Journal of Clinical Microbiology and Infectious Diseases Vol. 35; no. 12; pp. 1923 - 1931
• Main Author: Foster, T. J.
• Format: Journal Article Book Review
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2016; Springer Nature B.V
• Subjects: Adhesins, Bacterial - metabolism; Bacterial Adhesion; Biofilms; Biofilms - growth & development; Biomedical and Life Sciences; Biomedicine; Carrier Proteins - metabolism; Endocytosis; Fibronectins - metabolism; Internal Medicine; Medical Microbiology; Protein Binding; Protein Domains; Review; Staphylococcus aureus; Staphylococcus aureus - metabolism; Staphylococcus aureus - physiology; Fibronectin Binding; Prosthetic Joint Infection; Fibronectin Binding Protein; Septic Arthritis; Homophilic Interaction
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-016-2763-0

Staphylococcus aureus expresses two distinct but closely related multifunctional cell wall-anchored (CWA) proteins that bind to the host glycoprotein fibronectin. The fibronectin binding proteins FnBPA and FnBPB comprise two distinct domains. The C-terminal domain comprises a tandem array of repeats that bind to the N-terminal type I modules of fibronectin by the tandem β-zipper mechanism. This causes allosteric activation of a cryptic integrin binding domain, allowing fibronectin to act as a bridge between bacterial cells and the α 5 β 1 integrin on host cells, triggering bacterial uptake by endocytosis. Variants of FnBPA with polymorphisms in fibronectin binding repeats (FnBRs) that increase affinity for the ligand are associated with strains that infect cardiac devices and cause endocarditis, suggesting that binding affinity is particularly important in intravascular infections. The N-terminal A domains of FnBPA and FnBPB have diverged into seven antigenically distinct isoforms. Each binds fibrinogen by the ‘dock, lock and latch’ mechanism characteristic of clumping factor A. However, FnBPs can also bind to elastin, which is probably important in adhesion to connective tissue in vivo. In addition, they can capture plasminogen from plasma, which can be activated to plasmin by host and bacterial plasminogen activators. The bacterial cells become armed with a host protease which destroys opsonins, contributing to immune evasion and promotes spreading during skin infection. Finally, some methicillin-resistant S. aureus (MRSA) strains form biofilm that depends on the elaboration of FnBPs rather than polysaccharide. The A domains of the FnBPs can interact homophilically, allowing cells to bind together as the biofilm accumulates.