Staphylococcus aureus Clumping Factor A Binds to Complement Regulator Factor I and Increases Factor I Cleavage of C3b

• Published in: The Journal of Infectious Diseases 2008-07, Vol.198 (1), p.125-133
• Main Authors: Hair, Pamela S., Ward, Michael D., Semmes, O. John, Foster, Timothy J., Cunnion, Kenji M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies; Bacteria; Bacteriology; Biological and medical sciences; Cell walls; Chromatography; Coagulase - chemistry; Coagulase - immunology; Coagulase - metabolism; Complement C3b - immunology; Complement C3b - metabolism; Complement Factor I - metabolism; Enzyme linked immunosorbent assay; Fundamental and applied biological sciences. Psychology; Humans; Infections; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Monoclonal antibodies; Phagocytosis; Protein Binding; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - metabolism
• ISSN: 0022-1899; 1537-6591; 1537-6613
• DOI: 10.1086/588825

The human complement system plays an important role in the control of Staphylococcus aureus infection. For instance, we previously demonstrated that the central complement component deposited on the organism's surface, C3b, can be cleaved by the host complement control protein, factor I, resulting in diminished phagocytosis of S. aureus. In the present study, we have identified clumping factor A (ClfA) from cell wall proteins of S. aureus as a specific protein bound by factor I. Recombinant ClfA (rClfA) containing the full-length A region (peptides 40–559) also bound factor I. We identified an ∼50-kDa fragment of ClfA that is shed by S. aureus into growth medium. The shed ClfA fragment was derived from the A region of ClfA and bound factor I. rClfA and the shed ClfA fragment increased factor I cleavage of C3b into inactive C3b. Our findings describe a new S. aureus mechanism for modification of host complement activities.