Binding of Complement Inhibitor C4b-binding Protein to a Highly Virulent Streptococcus pyogenes M1 Strain Is Mediated by Protein H and Enhances Adhesion to and Invasion of Endothelial Cells

摘要: Streptococcus pyogenes AP1, a strain of the highly virulent M1 serotype, uses exclusively protein H to bind complement inhibitor C4b-binding (C4BP). We found strong correlation between ability AP1 and its isogenic mutants lacking inhibit opsonisation with C3b binding C4BP. C4BP bound immobilized or bacteria retained cofactor activity for degradation 125I-C4b. Further, C4b deposited from serum onto bacterial surfaces was processed into C4c/C4d fragments, which did not occur on strains unable Recombinant mutants, (i) lack certain CCP domains, (ii) have mutations in single aa as well (iii) additional different domains were used determine that is mainly mediated by patch positively charged amino acid residues at interface CCP1 CCP2. Using recombinant we narrowed down site N-terminal domain A. With peptide microarray, identified one 18 long comprising 92-109, specifically Biacore KD = 6x10-7 M subunit also correlated elevated levels adhesion invasion endothelial cells. Taken together, molecular basis C4BP-protein interaction it only important decreased but cells pyogenes. (Less)