Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin

C4BP (C4b-binding protein) is a high-molecular-weight plasma protein that inhibits the classical pathway of complement activation. Recent experiments have demonstrated that C4BP binds to many strains of the gram-positive bacterium Streptococcus pyogenes, a major respiratory tract pathogen. Binding to S. pyogenes was shown to be due to members of the M protein family, a group of surface proteins important for virulence. Here we report that human C4BP also binds to all clinical isolates of the gram-negative bacterium Bordetella pertussis, the etiologic agent of whooping cough. In addition, binding of C4BP was demonstrated for other Bordetella species that can cause disease in humans. Characterization of different B. pertussis mutants showed that the binding of C4BP is strongly dependent on the expression of the cell surface protein filamentous hemagglutinin, a well-known virulence factor. Inhibition experiments suggested that B. pertussis and S. pyogenes bind to the same region in C4BP. The finding that B. pertussis and S. pyogenes both have the ability to bind human C4BP suggests that these two unrelated respiratory tract pathogens may use a common mechanism during the establishment of an infection.

[1]  F. Greenwood,et al.  THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. , 1963, The Biochemical journal.

[2]  E. Hewlett,et al.  Soluble adenylate cyclase from the culture medium of Bordetella pertussis: purification and characterization , 1976, Journal of bacteriology.

[3]  V. Nussenzweig,et al.  Human C4-binding protein. I. Isolation and characterization , 1978, The Journal of experimental medicine.

[4]  V. Nussenzweig,et al.  Human C4-binding protein. II. Role in proteolysis of C4b by C3b- inactivator , 1978, The Journal of experimental medicine.

[5]  V. Nussenzweig,et al.  Presence of a C4-Binding Protein (C4-bp) in Human Serum , 1978 .

[6]  The fourth component of human complement treated with amines or chaotropes or frozen-thawed (C4b-like C4): interaction with C4 binding protein and cleavage by C3b/C4b inactivator. , 1982, Journal of immunology.

[7]  B. Dahlbäck.  Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. , 1983, The Biochemical journal.

[8]  E. Hewlett,et al.  Tn5-induced mutations affecting virulence factors of Bordetella pertussis , 1983, Infection and immunity.

[9]  V. Fischetti,et al.  Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[10]  B. Dahlbäck,et al.  Novel subunit in C4b-binding protein required for protein S binding. , 1988, The Journal of biological chemistry.

[11]  K. Joiner.  Complement evasion by bacteria and parasites. , 1988, Annual review of microbiology.

[12]  A. Melton,et al.  Use of the promoter fusion transposon Tn5 lac to identify mutations in Bordetella pertussis vir-regulated genes , 1989, Infection and immunity.

[13]  R. Rappuoli,et al.  Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Lindahl,et al.  Extensive sequence homology between IgA receptor and M proteins in Streptococcus pyogenes , 1989, Molecular microbiology.

[15]  D. Hourcade,et al.  The regulators of complement activation (RCA) gene cluster. , 1989, Advances in immunology.

[16]  D. Fearon,et al.  Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). , 1989, Advances in immunology.

[17]  D. Relman,et al.  Recognition of a bacterial adhesion by an integrin: macrophage CR3 (alpha M beta 2, CD11b/CD18) binds filamentous hemagglutinin of Bordetella pertussis. , 1990, Cell.

[18]  E. Ayoub,et al.  Microbial determinants of virulence and host response. , 1990 .

[19]  J. Mekalanos,et al.  Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis , 1991, Infection and immunity.

[20]  B. Dahlbäck.  Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C Anticoagulant System , 1991, Thrombosis and Haemostasis.

[21]  I. Charles,et al.  Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Barnum.  C4b-Binding protein, a regulatory protein of complement , 1991, Immunologic research.

[23]  F. Sundler,et al.  Plasma exudation as a first line respiratory mucosal defence , 1991, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[24]  F. Mooi,et al.  Construction and analysis of Bordetella pertussis mutants defective in the production of fimbriae. , 1992, Microbial pathogenesis.

[25]  C. Locht,et al.  Common accessory genes for the Bordetella pertussis filamentous hemagglutinin and fimbriae share sequence similarities with the papC and papD gene families. , 1992, The EMBO journal.

[26]  F. Mooi,et al.  Characterization of a Bordetella pertussis fimbrial gene cluster which is located directly downstream of the filamentous haemagglutinin gene , 1992, Molecular microbiology.

[27]  F. Mooi,et al.  Isolation of a putative fimbrial adhesin from Bordetella pertussis and the identification of its gene , 1993, Molecular Microbiology.

[28]  M. Andersson,et al.  Plasma exudation and solute absorption across the airway mucosa. , 1993, Clinical physiology.

[29]  C. Locht,et al.  The filamentous haemagglutinin, a multifaceted adhesin produced by virulent Bordetella spp. , 1993, Molecular microbiology.

[30]  D. Portnoy,et al.  Molecular Genetics of Bacterial Pathogenesis , 1994 .

[31]  R. Fernandez,et al.  Cloning and sequencing of a Bordetella pertussis serum resistance locus , 1994, Infection and immunity.

[32]  C. Locht,et al.  Mutational analysis of the Bordetella pertussis fim/fha gene cluster: identification of a gene with sequence similarities to haemolysin accessory genes involved in export of FHA , 1994, Molecular microbiology.

[33]  J. Bergelson,et al.  Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[34]  F. Mooi.  Genes for the Filamentous Hemagglutinin and Fimbriae of Bordetella pertussis: Colocation, Coregulation, and Cooperation? , 1994 .

[35]  M. Kehoe.  Chapter 11 Cell-wall-associated proteins in Gram-positive bacteria , 1994 .

[36]  P. Minor,et al.  Decay‐accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno‐focal cloning method. , 1994, The EMBO journal.

[37]  J. Atkinson,et al.  Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[38]  T. Finn,et al.  Tracheal colonization factor: a Bordetella pertussis secreted virulence determinant , 1995, Molecular microbiology.

[39]  M. Dierich,et al.  Interaction of several complement proteins with gp120 and gp41, the two envelope gycoproteins of HIV‐1 , 1995, AIDS.

[40]  K. Nakamura,et al.  Human factor H and C4b-binding protein serve as factor I-cofactors both encompassing inactivation of C3b and C4b. , 1995, Molecular immunology.

[41]  G. Lindahl,et al.  Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system. , 1995, Journal of immunology.

[42]  D. Gerlier,et al.  CD46-mediated measles virus entry: a first key to host-range specificity. , 1995, Trends in microbiology.

[43]  E. Johnsson,et al.  A highly variable region in members of the streptococcal M protein family binds the human complement regulator C4BP. , 1996, Journal of immunology.

[44]  R. Parton.  New perspectives on Bordetella pathogenicity. , 1996, Journal of medical microbiology.

[45]  Jeff F. Miller,et al.  Understanding signal transduction during bacterial infection. , 1996, Trends in microbiology.

[46]  S. Rodríguez de Córdoba,et al.  Binding of human complement component C4b-binding protein (C4BP) to Streptococcus pyogenes involves the C4b-binding site. , 1996, Journal of immunology.

[47]  R. Rappuoli.  Acellular pertussis vaccines: a turning point in infant and adolescent vaccination. , 1996, Infectious agents and disease.

[48]  C. Locht,et al.  Amino‐terminal maturation of the Bordetella pertussis filamentous haemagglutinin , 1996, Molecular microbiology.

[49]  B. Dahlbäck,et al.  The amino-terminal module of the C4b-binding protein alpha-chain is crucial for C4b binding and factor I-cofactor function. , 1997, The Biochemical journal.