title: Binding of human factor H to outer membrane protein P5 of non-typeable Haemophilus influenzae contributes to complement resistance.
abstract: Non-typeable Haemophilus influenzae is an opportunistic pathogen of the human upper respiratory tract and is often found to cause inflammatory diseases that include sinusitis, otitis media and exacerbations of chronic obstructive pulmonary disease. To persist in the inflammatory milieu during infection, non-typeable H. influenzae must resist the antimicrobial activity of the human complement system. Here, we used Tn-seq to identify genes important for resistance to complement-mediated killing. This screen identified outer membrane protein P5 in evasion of the alternative pathway of complement activation. Outer membrane protein P5 was shown to bind human complement regulatory protein factor H directly, thereby, preventing complement factor C3 deposition on the surface of the bacterium. Furthermore, we show that amino acid variation within surface-exposed regions within outer membrane P5 affected the level of factor H binding between individual strains.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeroen D
authors.initials: JD
authors.lastname: Langereis
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D003176:Complement C3 / Q000276:immunology*; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D006192:Haemophilus Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans
chemical_list: D001425:Bacterial Outer Membrane Proteins; C493495:CFH protein, human; D003176:Complement C3; C082912:outer membrane protein P5, Haemophilus; D017242:Complement Factor H
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