title: Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity.
abstract: Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most of the effect, and the Moraxella mutant lacking UspA2 was more sensitive to the lytic effect of human serum compared with the wild type. Interestingly, among the large number of bacteria analyzed, only M. catarrhalis has this unique ability to interfere with the innate immune system of complement by binding C3.
authors.affiliation: Medical Microbiology, Lund University, Malmo University Hospital, Malmo, Sweden.
authors.forename: Therése
authors.initials: T
authors.lastname: Nordström
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Thuan Tong
authors.initials: TT
authors.lastname: Tan
authors.forename: Arne
authors.initials: A
authors.lastname: Forsgren
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D001770:Blood Bactericidal Activity; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D001936:Moraxella catarrhalis / Q000276:immunology / Q000472:pathogenicity*; D011485:Protein Binding / Q000276:immunology; D055672:Static Electricity
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003176:Complement C3; C089675:UspA protein, Moraxella catarrhalis