TY  - JOUR
A1  - Hart, Thomas
A1  - Nguyen, Ngoc Thien Thu
A1  - Nowak, Nancy A.
A1  - Zhang, Fuming
A1  - Linhardt, Robert J.
A1  - Diuk-Wasser, Maria A.
A1  - Ram, Sanjay
A1  - Kraiczy, Peter
A1  - Lin, Yi-Pin
T1  - Polymorphic factor H-binding activity of CspA protects Lyme borreliae from the host complement in feeding ticks to facilitate tick-to-host transmission
T2  - PLoS pathogens
N2  - Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA-knockout B. burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B. burgdorferi or B. afzelii, but not B. garinii in a cspA-knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3-/- mice that lacked functional complement. The cspA-knockout B. burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B. burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.
KW  - Borrelia burgdorferi
KW  - Nymphs
KW  - Spirochetes
KW  - Horses
KW  - Complement system
KW  - Blood
KW  - Flow cytometry
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46592
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-465920
SN  - 1553-7374
SN  - 1553-7366
N1  - This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
VL  - 14
IS  - (5): e1007106
SP  - 1
EP  - 35
PB  - PLoS
CY  - Lawrence, Kan.
ER  -