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LfhA, a Novel Factor H-Binding Protein of Leptospira interrogans

Ashutosh Verma,¹ Jens Hellwage,^2, Sergey Artiushin,¹ Peter F. Zipfel,² Peter Kraiczy,³ John F. Timoney,¹ and Brian Stevenson^4*

Gluck Equine Research Center, University of Kentucky, Lexington, Kentucky 40546,¹ Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena D-07745, Germany,² Institute of Medical Microbiology, University Hospital of Frankfurt, Frankfurt D-60596, Germany,³ Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky 40536⁴

Received 29 November 2005/ Returned for modification 2 January 2006/ Accepted 1 February 2006

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.

Editor: D. L. Burns

Present address: 4-Antibody AG, Bioinstrumentezentrum, Winzerlaer Strasse 2, D-07745 Jena, Germany.

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