TY  - JOUR
A1  - Hart, Thomas M.
A1  - Dupuis, Alan P. II
A1  - Tufts, Danielle M.
A1  - Blom, Anna M.
A1  - Starkey, Simon R.
A1  - Rego, Ryan O. M.
A1  - Ram, Sanjay
A1  - Kraiczy, Peter
A1  - Kramer, Laura D.
A1  - Diuk-Wasser, Maria A.
A1  - Kolokotronis, Sergios-Orestis
A1  - Lin, Yi-Pin
T1  - Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system
T2  - PLoS pathogens
N2  - Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62702
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-627029
SN  - 1553-7374
N1  - This work was supported by NIH U01CK000509, NSF IOS1755370 (DMT and MDW), NSF IOS1754995 (SOK), NSF IOS1755286 (YPL, ADII, LDK, and TMH), DoD TB170111, NIH R21AI144891, NIH R21AI146381, New York State Department of Health Wadsworth Center Start-Up Grant (TMH and YPL), the Czech Science Foundation grant No. 17-21244S (ROMR), and the LOEWE Center DRUID Novel Drug Targets against Poverty-Related and Neglected Tropical Infectious Diseases, project C3 (PK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
VL  - 17
IS  - 7, art. e1009801
SP  - 1
EP  - 29
PB  - PLoS
CY  - Lawrence, Kan.
ER  -