The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus

Area of Science:

• Microbiology
• Molecular Biology
• Infectious Diseases

Background:

• Staphylococcus aureus utilizes cell wall-anchored (CWA) proteins, specifically fibronectin binding proteins (FnBPs), to interact with host tissues.
• FnBPs mediate bacterial adhesion, immune evasion, and biofilm formation, crucial for S. aureus pathogenesis.

Purpose of the Study:

• To elucidate the multifaceted roles of FnBPA and FnBPB in Staphylococcus aureus pathogenesis.
• To investigate the mechanisms by which FnBPs mediate bacterial adhesion, host cell entry, and immune evasion.

Main Methods:

• Analysis of FnBP domains and their interactions with host ligands like fibronectin and fibrinogen.
• Investigation of FnBP contributions to bacterial uptake, immune evasion via plasminogen capture, and biofilm formation.
• Correlation of fibronectin binding repeat (FnBR) polymorphisms with clinical outcomes in intravascular infections.

Main Results:

• FnBPs bind fibronectin via C-terminal repeats, activating host integrins for bacterial endocytosis.
• N-terminal A domains bind fibrinogen and elastin, and capture host plasminogen, facilitating immune evasion and tissue spread.
• Enhanced fibronectin binding affinity is associated with severe endocarditis and cardiac device infections.
• FnBPs are essential for biofilm formation in some methicillin-resistant S. aureus (MRSA) strains through homophilic interactions.

Conclusions:

• FnBPs are critical virulence factors with diverse functions, enabling S. aureus to colonize, invade, and persist within the host.
• Targeting FnBP interactions presents a potential strategy for combating S. aureus infections, particularly those involving biofilms and intravascular devices.