In:
Molecular Microbiology, Wiley, Vol. 99, No. 2 ( 2016-01), p. 407-424
Kurzfassung:
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 .
Materialart:
Online-Ressource
ISSN:
0950-382X
,
1365-2958
DOI:
10.1111/mmi.2016.99.issue-2
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2016
ZDB Id:
1501537-3
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