Date of Award




Document Type


Degree Name

Doctor of Philosophy (PhD)


Department of Biological Sciences

Content Description

1 online resource (ix, 221 pages) : color illustrations.

Dissertation/Thesis Chair

Yi-Pin Lin

Committee Members

Ing-Nang Wang, Sergios-Orestis Kolokotronis, Maria A Diuk-Wasser


Borrelia, Complement, Convergent evolution, Host specialization, Lyme disease, Ticks, Borrelia burgdorferi, Animals as carriers of disease, Ticks as carriers of disease, Vector-pathogen relationships, Host-parasite relationships

Subject Categories

Ecology and Evolutionary Biology | Evolution | Microbiology


Vector-borne diseases, such as Lyme disease caused by Borrelia burgdorferi sensu lato (Bbsl), have narrow host ranges and are apt models to study host-microparasite coevolution. Some species and strains of Lyme borreliae (LB) are specialists, infecting only mammalian or only avian hosts (ex. Borrelia afzelii and B. garinii, respectively), while others are generalists and infect both hosts (ex. B. burgdorferi). Such host tropisms are hypothesized to be partially shaped by the ability of these pathogens evade host immune defenses, such as complement. Complement is a first line host defense against invading pathogens that kills LB in vitro and inhibits spirochete infection in vivo. In fact, complement can be activated within hours upon spirochete invasion, and different species and strains of LB vary in their ability to evade complement of different host species. We thus hypothesized tick-to-host transmission of LB is dependent on the spirochetes’ ability to evade complement-mediated killing in tick blood meals, and that variation in this ability leads to host-specific transmission. It is difficult to study host-specific survival in the blood meals taken from relevant hosts due to issues with maintaining and using wild-caught or atypical animal models representing natural reservoir hosts, such as the lack of proper facilities or appropriate reagents. We overcome these issues with an artificial membrane feeding model, which allows us to feed ticks on blood of different vertebrate hosts and manipulate the complement in the blood. We used this model and live host models to investigate the impact of complement on tick-to-host transmission by feeding I. scapularis nymphs infected with B. burgdorferi ss, B. garinii, or B. afzelii on avian or mammalian blood and hosts, with or without complement. We observed differences in these strains’ ability to survive complement in feeding ticks and transmit to hosts or blood. These differences correlated with aforementioned host tropisms, indicating the source of complement in the blood meal dictates tick-to-host transmission success defining LB host tropisms. We next sought to determine the molecular mechanisms by which complement defines host tropisms. We focused on a polymorphic spirochete-produced protein, CspA, as this protein is produced when spirochetes are in ticks, and binds to the host complement inhibitor, Factor H (FH), to facilitate spirochete complement evasion in vitro. When we fed ticks carrying isogenic strains of B. burgdorferi ss producing different CspA variants on mammalian and avian blood and hosts, we found isogenic strains producing CspA variants of B. burgdorferi ss, B. garinii, and B. afzelii differed in their ability to facilitate LB complement evasion in a feeding tick and tick-to-host transmission. These findings mirrored the same phenotypes of the wildtype spirochetes from which the CspA variants were derived, demonstrating the CspA-FH binding activity is the molecular mechanism behind the host-specific transmission. CspA is a member of a paralogous protein family, leading to the hypothesis other family members bind FH as well. However, we found FH-binding is unique to CspA. We then compared nucleotide sequences of cspA and identified spirochete genospecies-specific nucleotide sequence polymorphisms. Additionally, variants from different LB strains of the same genospecies share a notably high degree of sequence identity, implying that these confer similar FH-binding and transmission phenotypes. We then examined the phylogeny of this protein family and found that the FH-binding activity of CspA arose through convergent evolution at the end of the last glacial maximum, indicating a shift in the Lyme enzootic cycle necessitating this complement evasion strategy. Overall, these studies provide tools to study LB host tropisms, describe the underlying mechanisms, and give insight into the evolution of the enzootic cycle. Further, this work lays the foundation for future investigations into molecular and evolutionary bases of host tropisms and the origins of enzootic cycles of other vector-borne diseases.