Mechanism of Borrelia immune evasion by FhbA-related proteins.

Autor: Kogan K; HiLife Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Haapasalo K; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland., Kotila T; HiLife Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Moore R; Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland., Lappalainen P; HiLife Institute of Biotechnology, University of Helsinki, Helsinki, Finland., Goldman A; Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.; Astbury Center for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom., Meri T; Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Mar 18; Vol. 18 (3), pp. e1010338. Date of Electronic Publication: 2022 Mar 18 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010338
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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