title: Disruption of the alternative pathway convertase occurs at the staphylococcal surface via the acquisition of factor H by Staphylococcus aureus.
abstract: Staphylococcus aureus is a significant human pathogen that causes skin-structure, invasive, and hospital-associated infections worldwide. The complement system is vital to innate defense against many bacterial infections. As shown with other pathogens, mechanisms for circumventing complement attack may include recruitment of the complement regulatory protein factor H (fH). In the present study, we show that S. aureus binds fH in a dose-dependent and time-dependent manner. Interestingly, this interaction does not require complement activation nor C3-fragment presence and occurs efficiently in the absence of other serum components suggesting a mechanism other than bridging between intermediary molecules. However, fH binding is greater when incubated with normal human serum compared to heat-inactivated serum, which suggests that complement activation may enhance fH binding. S. aureus-bound fH was found to inhibit the alternative pathway through disruption of the alternative pathway C3 convertase as shown by an increase in Bb release and a decrease in total C3-fragment deposition. Furthermore, S. aureus-bound fH retains cofactor activity for factor-I mediated cleavage of C3b. These studies show that the acquisition of fH to the S. aureus surface inhibits complement-mediated opsonization via disruption of the alternative pathway convertase; thus, we report an immune-evasion mechanism not previously described for S. aureus.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA 23501-1980, USA. sharpja@evms.edu
authors.forename: Julia A
authors.initials: JA
authors.lastname: Sharp
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
mesh_terms: D002462:Cell Membrane / Q000276:immunology*; D051561:Complement C3 Convertase, Alternative Pathway / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology*; D003170:Complement Pathway, Alternative / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000166:cytology* / Q000254:growth & development / Q000276:immunology*; D013997:Time Factors
chemical_list: D003179:Complement C3b; D017242:Complement Factor H; D005340:Fibrinogen; D051561:Complement C3 Convertase, Alternative Pathway