4.5 Review

The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus

Journal

Publisher

SPRINGER
DOI: 10.1007/s10096-016-2763-0

Keywords

-

Ask authors/readers for more resources

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 beta-zipper mechanism. This causes allosteric activation of a cryptic integrin binding domain, allowing fibronectin to act as a bridge between bacterial cells and the alpha(5)beta(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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available