title: Complement regulator C4BP binds to Staphylococcus aureus and decreases opsonization.
abstract: Staphylococcus aureus is the major cause of human skin and soft-tissue infections as well as invasive infections like post-operative wound infections, septic arthritis, and osteomyelitis. The complement system plays an important role in the immunological control of many bacteria, but can be inhibited by a variety of strategies including recruitment of complement regulatory proteins like C4b-binding protein (C4BP). These experiments demonstrate that S. aureus opsonization with C4b occurs rapidly in serum and is predominantly initiated by anti-staphylococcal antibodies. Much of the S. aureus-bound C4b is quickly cleaved to the inactive forms iC4b and C4d. Clinical S. aureus strains rapidly bind significant amounts of the complement regulator C4BP from serum. S. aureus also binds purified C4BP. S. aureus-bound C4BP functions as a cofactor for factor I-mediated C4b cleavage to iC4b and C4d. In the absence of factor I, C4BP decreases classical pathway-mediated deposition of C3b on the S. aureus surface by inhibiting the classical pathway C3-convertase. In summary, C4BP is recruited to the S. aureus surface where it functions to inhibit C4 complement effectors, suggesting a previously undescribed immune evasion strategy for this pathogen.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23501-1980, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hair
authors.forename: Sara M
authors.initials: SM
authors.lastname: Wagner
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Friederich
authors.forename: Richard R
authors.initials: RR
authors.lastname: Drake
authors.forename: Julius O
authors.initials: JO
authors.lastname: Nyalwidhe
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D015153:Blotting, Western; D003167:Complement Activation / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology*; D050716:Complement C4b-Binding Protein; D004797:Enzyme-Linked Immunosorbent Assay; D006649:Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D013058:Mass Spectrometry; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; C055609:C4BPA protein, human; D003181:Complement C4; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens