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BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by inhibiting assembly of the membrane attack complex
Author(s) -
Hammerschmidt Claudia,
Klevenhaus Yvonne,
Koenigs Arno,
Hallström Teresia,
Fingerle Volker,
Skerka Christine,
Pos Klaas Martinus,
Zipfel Peter F.,
Wallich Reinhard,
Kraiczy Peter
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13239
Subject(s) - biology , complement system , innate immune system , factor h , complement membrane attack complex , complement control protein , alternative complement pathway , classical complement pathway , effector , microbiology and biotechnology , complement component 2 , borrelia , immune system , antibody , genetics , borrelia burgdorferi
Summary Borrelia ( B .) bavariensis exhibits a marked tropism for nervous tissues and frequently causes neurological manifestations in humans. The molecular mechanism by which B . bavariensis overcomes innate immunity, in particular, complement remains elusive. In contrast to other serum‐resistant spirochetes, none of the B . bavariensis isolates investigated bound complement regulators of the alternative ( AP ) and classical pathway ( CP ) or proteolytically inactivated complement components. Focusing on outer surface proteins BGA 66 and BGA 71, we demonstrated that both molecules either inhibit AP , CP and terminal pathway ( TP ) activation, or block activation of the CP and TP respectively. Both molecules bind complement components C 7, C 8 and C 9, and thereby prevent assembly of the terminal complement complex. This inhibitory activity was confirmed by the introduction of the BGA 66 and BGA 71 encoding genes into a serum‐sensitive B . garinii strain. Transformed spirochetes producing either BGA 66 or BGA 71 overcome complement‐mediated killing, thus indicating that both proteins independently facilitate serum resistance of B . bavariensis . The generation of C ‐terminally truncated proteins as well as a chimeric BGA 71 protein lead to the localization of the complement‐interacting binding site within the N ‐terminus. Collectively, our data reveal a novel immune evasion strategy of B . bavariensis that is directed against the activation of the TP .