Staphylococcus aureus clumping factor A binds to complement regulator factor I and increases factor I cleavage of C3b

Area of Science:

• Immunology
• Microbiology
• Bacterial Pathogenesis

Background:

• The human complement system is crucial for controlling Staphylococcus aureus infections.
• Previous work showed complement component C3b deposition on S. aureus leads to phagocytosis, but this can be inhibited.
• Factor I, a host complement control protein, cleaves C3b, reducing S. aureus phagocytosis.

Purpose of the Study:

• To identify specific S. aureus proteins that interact with the host complement control protein, factor I.
• To elucidate a novel mechanism by which S. aureus modifies host complement activity.

Main Methods:

• Identification of S. aureus cell wall proteins bound by factor I.
• Characterization of recombinant ClfA (rClfA) and shed ClfA fragments.
• Assays to measure factor I-mediated cleavage of C3b in the presence of rClfA and shed ClfA.

Main Results:

• Clumping factor A (ClfA), a cell wall protein of S. aureus, was identified as a specific binding protein for factor I.
• Both recombinant full-length ClfA (rClfA) and a 50-kDa shed ClfA fragment bound factor I.
• rClfA and the shed ClfA fragment significantly enhanced factor I-mediated cleavage of C3b into inactive C3b, thereby promoting immune evasion.

Conclusions:

• S. aureus employs ClfA as a mechanism to interfere with the host complement system.
• Binding of factor I by ClfA facilitates the inactivation of C3b, representing a novel immune evasion strategy for S. aureus.