title: Clinical isolates of Streptococcus pneumoniae bind the complement inhibitor C4b-binding protein in a PspC allele-dependent fashion.
abstract: The complement system constitutes an important component of the innate immune system. To colonize their host and/or to cause disease, many pathogens have evolved strategies to avoid complement-mediated bacterial lysis and opsonophagocytosis. In this study, using a collection of 55 clinical isolates of Streptococcus pneumoniae, we demonstrate for the first time that pneumococci bind the complement inhibitor C4b-binding protein (C4BP). C4BP binding seems to be restricted to certain serotypes such as serotype 4, 6B, 7F, and 14, of which the strains of serotype 14 are the strongest binders. We show that bacteria-bound C4BP retains its functional activity and down-regulates the activation of the classical pathway. Thus, this major respiratory pathogen may escape immune recognition and eradication by the complement system. Furthermore, we show that C4BP binding varies between strains but is dependent on the expression of pneumococcal surface protein C, PspC of group 4. The study of the distribution of group 4 pspC locus shows that most of high-binder serotype 14 isolates harbor an allelic variant of group 4 pspC. Using PspC-negative mutant strains, we identified a new allelic variant of PspC (PspC4.4) as a major ligand for C4BP, revealing a new function for this important pneumococcal virulence factor. Thus pneumococci exploit host C4BP for complement evasion in a PspC allele-dependent manner.
authors.affiliation: Department of Laboratory Medicine, Medical Microbiology, Lund University, Malmö, Sweden.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dieudonné-Vatran
authors.forename: Stefanie
authors.initials: S
authors.lastname: Krentz
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.forename: Barbara
authors.initials: B
authors.lastname: Albiger
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D050716:Complement C4b-Binding Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D050716:Complement C4b-Binding Protein; D008024:Ligands; C110344:SpsA protein, Streptococcus pneumoniae