Mechanism of Borrelia immune evasion by FhbA-related proteins |
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| Authors: | Konstantin Kogan Karita Haapasalo Tommi Kotila Robin Moore Pekka Lappalainen Adrian Goldman Taru Meri |
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| Affiliation: | 1. HiLife Institute of Biotechnology, University of Helsinki, Helsinki, Finland;2. Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland;3. Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland;4. Astbury Center for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; Medical College of Wisconsin, UNITED STATES |
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| Abstract: | Immune evasion facilitates survival of Borrelia, leading to infections like relapsing fever and Lyme disease. Important mechanism for complement evasion is acquisition of the main host complement inhibitor, factor H (FH). By determining the 2.2 Å crystal structure of Factor H binding protein A (FhbA) from Borrelia hermsii in complex with FH domains 19–20, combined with extensive mutagenesis, we identified the structural mechanism by which B. hermsii utilizes FhbA in immune evasion. Moreover, structure-guided sequence database analysis identified a new family of FhbA-related immune evasion molecules from Lyme disease and relapsing fever Borrelia. Conserved FH-binding mechanism within the FhbA-family was verified by analysis of a novel FH-binding protein from B. duttonii. By sequence analysis, we were able to group FH-binding proteins of Borrelia into four distinct phyletic types and identified novel putative FH-binding proteins. The conserved FH-binding mechanism of the FhbA-related proteins could aid in developing new approaches to inhibit virulence and complement resistance in Borrelia. |
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