| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland;
Evans Biomedical Research Center, Boston Medical Center, Boston, MA 02118;
Institute for Hygiene and Microbiology, University of Wurzburg, Wurzburg, Germany; and
Lund University, Department of Clinical Chemistry, University Hospital Malmö, Malmö, Sweden
Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.
This article has been cited by other articles:
|
|
 |
|
  L. A. Lewis, S. Ram, A. Prasad, S. Gulati, S. Getzlaff, A. M. Blom, U. Vogel, and P. A. Rice Defining Targets for Complement Components C4b and C3b on the Pathogenic Neisseriae Infect. Immun., January 1, 2008; 76(1): 339 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jarva, J. Ngampasutadol, S. Ram, P. A. Rice, B. O. Villoutreix, and A. M. Blom Molecular Characterization of the Interaction between Porins of Neisseria gonorrhoeae and C4b-Binding Protein J. Immunol., July 1, 2007; 179(1): 540 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hallstrom, H. Jarva, K. Riesbeck, and A. M. Blom Interaction with C4b-Binding Protein Contributes to Nontypeable Haemophilus influenzae Serum Resistance J. Immunol., May 15, 2007; 178(10): 6359 - 6366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Madico, J. Ngampasutadol, S. Gulati, U. Vogel, P. A. Rice, and S. Ram Factor H Binding and Function in Sialylated Pathogenic Neisseriae is Influenced by Gonococcal, but Not Meningococcal, Porin J. Immunol., April 1, 2007; 178(7): 4489 - 4497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kahler, S. Lyons-Schindler, B. Choudhury, J. Glushka, R. W. Carlson, and D. S. Stephens O-Acetylation of the Terminal N-Acetylglucosamine of the Lipooligosaccharide Inner Core in Neisseria meningitidis: INFLUENCE ON INNER CORE STRUCTURE AND ASSEMBLY J. Biol. Chem., July 21, 2006; 281(29): 19939 - 19948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Madico, J. A. Welsch, L. A. Lewis, A. McNaughton, D. H. Perlman, C. E. Costello, J. Ngampasutadol, U. Vogel, D. M. Granoff, and S. Ram The Meningococcal Vaccine Candidate GNA1870 Binds the Complement Regulatory Protein Factor H and Enhances Serum Resistance J. Immunol., July 1, 2006; 177(1): 501 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Schneider, R. M. Exley, H. Chan, I. Feavers, Y.-H. Kang, R. B. Sim, and C. M. Tang Functional Significance of Factor H Binding to Neisseria meningitidis. J. Immunol., June 15, 2006; 176(12): 7566 - 7575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Attia, S. Ram, P. A. Rice, and E. J. Hansen Binding of Vitronectin by the Moraxella catarrhalis UspA2 Protein Interferes with Late Stages of the Complement Cascade Infect. Immun., March 1, 2006; 74(3): 1597 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Jenkins, L. Mark, G. Ball, J. Persson, G. Lindahl, D. Uhrin, A. M. Blom, and P. N. Barlow Human C4b-binding Protein, Structural Basis for Interaction with Streptococcal M Protein, a Major Bacterial Virulence Factor J. Biol. Chem., February 10, 2006; 281(6): 3690 - 3697. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
