title: Functional significance of factor H binding to Neisseria meningitidis.
abstract: Neisseria meningitidis is an important cause of septicemia and meningitis. To cause disease, the bacterium must successfully survive in the bloodstream where it has to avoid being killed by host innate immune mechanisms, particularly the complement system. A number of pathogenic microbes bind factor H (fH), the negative regulator of the alternative pathway of complement activation, to promote their survival in vivo. In this study, we show that N. meningitidis binds fH to its surface. Binding to serogroups A, B, and C N. meningitidis strains was detected by FACS and Far Western blot analysis, and occurred in the absence of other serum factors such as C3b. Unlike Neisseria gonorrhoeae, binding of fH to N. meningitidis was independent of sialic acid on the bacterium, either as a component of its LPS or its capsule. Characterization of the major fH binding partner demonstrated that it is a 33-kDa protein; examination of insertion mutants showed that porins A and B, outer membrane porins expressed by N. meningitidis, do not contribute significantly to fH binding. We examined the physiological consequences of fH bound to the bacterial surface. We found that fH retains its activity as a cofactor of factor I when bound to the bacterium and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. Therefore, the recruitment of fH provides another mechanism by which this important human pathogen evades host innate immunity.
authors.affiliation: Centre for Molecular Microbiology and Infection, Imperial College London, UK.
authors.forename: Muriel C
authors.initials: MC
authors.lastname: Schneider
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Exley
authors.forename: Hannah
authors.initials: H
authors.lastname: Chan
authors.forename: Ian
authors.initials: I
authors.lastname: Feavers
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000276:immunology*; D016667:Bacterial Capsules / Q000378:metabolism / Q000502:physiology; D001770:Blood Bactericidal Activity / Q000276:immunology; D026481:Blotting, Far-Western; D017242:Complement Factor H / Q000378:metabolism / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019158:N-Acetylneuraminic Acid / Q000378:metabolism / Q000502:physiology; D009345:Neisseria meningitidis / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D018272:Porins / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000276:immunology
chemical_list: D018272:Porins; C057699:porin protein, Neisseria; D017242:Complement Factor H; D019158:N-Acetylneuraminic Acid