title: Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles.
abstract: Moraxella catarrhalis causes respiratory tract infections in children and in adults with chronic obstructive pulmonary disease. It is often isolated as a copathogen with Haemophilus influenzae. The underlying mechanism for this cohabitation is unclear. Here, in clinical specimens from a patient with M. catarrhalis infection, we document that outer membrane vesicles (OMVs) carrying ubiquitous surface protein (Usp) A1 and UspA2 (hereafter, UspA1/A2) were secreted. Further analyses revealed that OMVs isolated in vitro also contained UspA1/A2, which mediate interactions with, among other proteins, the third component of the complement system (C3). OMVs from M. catarrhalis wild-type clinical strains bound to C3 and counteracted the complement cascade to a larger extent than did OMVs without UspA1/A2. In contrast, UspA1/A2-deficient OMVs were significantly weaker inhibitors of complement-dependent killing of H. influenzae. Thus, our results suggest that a novel strategy exists in which pathogens collaborate to conquer innate immunity and that the M. catarrhalis vaccine candidates UspA1/A2 play a major role in this interaction.
authors.affiliation: Medical Microbiology, Department of Laboratory Medicine, Malmo University Hospital, Lund University, Malmo, Malmo, Sweden.
authors.forename: Thuan Tong
authors.initials: TT
authors.lastname: Tan
authors.forename: Matthias
authors.initials: M
authors.lastname: Morgelin
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 / Q000235:genetics / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D021961:Cell Membrane Structures / Q000378:metabolism* / Q000648:ultrastructure; D002648:Child; D003176:Complement C3 / Q000378:metabolism; D003470:Culture Media; D006193:Haemophilus influenzae / Q000254:growth & development* / Q000472:pathogenicity*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D001936:Moraxella catarrhalis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000648:ultrastructure*; D045828:Moraxellaceae Infections / Q000382:microbiology; D009154:Mutation; D012852:Sinusitis / Q000382:microbiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003176:Complement C3; D003470:Culture Media; C089675:UspA protein, Moraxella catarrhalis