Open AccessMechanism of Borrelia immune evasion by FhbA-related proteins
Author(s) -
Konstantin Kogan,
Karita Haapasalo,
Tommi Kotila,
Robin Moore,
Pekka Lappalainen,
Adrian Goldman,
Taru Meri
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010338
Subject(s) - evasion (ethics) , mechanism (biology) , immune system , borrelia , biology , microbiology and biotechnology , virology , computational biology , borrelia burgdorferi , immunology , antibody , philosophy , epistemology
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 .