title: Differences in complement activation between complement-resistant and complement-sensitive Moraxella (Branhamella) catarrhalis strains occur at the level of membrane attack complex formation.
abstract: The mechanism of resistance to human complement-mediated killing in Moraxella catarrhalis was studied by comparing different complement-sensitive and complement-resistant M. catarrhalis strains in a functional bystander hemolysis assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal complement complexes. Complement-resistant stains appeared to activate complement to the same extent as, or even slightly better than, complement-sensitive strains. This indicates that complement-resistant strains do not inhibit classical or alternative pathway activation but interfere with complement at the level of membrane attack complex formation. A clear difference in dose-response curves for resistant and sensitive strains was observed both in the bystander hemolysis assay and in the ELISA. Complement-resistant strains showed optimum curves, whereas complement-sensitive strains gave almost linear curves. We conclude that resistant strains bind and/or inactivate one of the terminal complement components or intermediates involved in membrane attack complex formation. Trypsin, known to abolish complement resistance, changed the optimum dose-response curve of a resistant strain to a linear one, which strongly suggests that complement resistance is mediated by an M. catarrhalis-associated protein. This protein acts directly or through the binding of a terminal complement inhibitor present in serum.
authors.affiliation: Eijkman-Winkler Institute of Medical and Clinical Microbiology, Utrecht University Medical Faculty, University Hospital, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Verduin
authors.forename: M
authors.initials: M
authors.lastname: Jansze
authors.forename: C
authors.initials: C
authors.lastname: Hol
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: H
authors.initials: H
authors.lastname: van Dijk
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D001936:Moraxella catarrhalis / Q000276:immunology*; D013045:Species Specificity
chemical_list: D001426:Bacterial Proteins; D015938:Complement Membrane Attack Complex