title: LfhA, a novel factor H-binding protein of Leptospira interrogans.
abstract: The early phase of leptospiral infection is characterized by the presence of live organisms in the blood. Pathogenic Leptospira interrogans is resistant to the alternative pathway of complement mediated-killing, while nonpathogenic members of the genus are not. Consistent with that observation, only pathogenic leptospires bound factor H, a host fluid-phase regulator of the alternative complement pathway. Ligand affinity blot analyses revealed that pathogenic L. interrogans produces at least two factor H-binding proteins. Through screening of a lambda phage expression library, we identified one of these as the novel membrane protein LfhA. Ligand affinity assays and surface plasmon resonance analyses of recombinant LfhA revealed specific binding of both factor H and factor H-related protein 1. Serological examination of infected humans and horses demonstrated that LfhA is expressed by L. interrogans during mammalian infection. LfhA may therefore contribute to the resistance of pathogenic leptospires to complement-mediated killing during leptospiremic phases of the disease.
authors.affiliation: Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Verma
authors.forename: Jens
authors.initials: J
authors.lastname: Hellwage
authors.forename: Sergey
authors.initials: S
authors.lastname: Artiushin
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
authors.forename: John F
authors.initials: JF
authors.lastname: Timoney
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001428:Bacterial Vaccines / Q000276:immunology; D001483:Base Sequence; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D017242:Complement Factor H / Q000378:metabolism*; D006736:Horses; D007921:Leptospira interrogans / Q000276:immunology*; D008969:Molecular Sequence Data
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D001798:Blood Proteins; D002352:Carrier Proteins; C100631:factor H-related protein 1; D017242:Complement Factor H