Pathogenic bacteria attach to human fibronectin through a tandem beta-zipper

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Staphylococcus aureus and Streptococcus pyogenes are significant human pathogens.
• These bacteria adhere to and invade host cells by targeting host fibronectin (Fn).
• Bacterial fibronectin-binding proteins (FnBPs) mediate this interaction via Fn-binding repeats.

Purpose of the Study:

• To elucidate the structural mechanism by which streptococcal FnBP peptides bind fibronectin modules.
• To understand how bacterial FnBPs exploit fibronectin's modular structure for host cell invasion.

Main Methods:

• X-ray crystallography was used to determine the structure of a streptococcal FnBP peptide (B3) bound to fibronectin modules (1F12F1).
• Sequence analysis was performed on FnBPs from S. pyogenes and S. aureus.

Main Results:

• The structure revealed novel 1F1- and 2F1-binding motifs in the FnBP peptide.
• These motifs form antiparallel beta-strands on sequential fibronectin modules, creating a tandem beta-zipper.
• Sequence analysis showed repeating F1-binding motifs in bacterial FnBPs that mirror fibronectin's F1 module pattern.

Conclusions:

• Bacterial FnBPs utilize a tandem beta-zipper mechanism to bind fibronectin modules.
• This binding strategy exploits the modular nature of fibronectin for efficient host cell invasion.
• The findings provide crucial insights into the mechanism of integrin-dependent FnBP-mediated bacterial invasion.