Date of Award

January 2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

First Advisor

Catherine A. Brissette

Abstract

The Borrelia burgdorferi sensu lato (s.l.) complex contains species carried by hard-shell ticks (Ixodes spp.) and causing Lyme disease and related non-pathogenic species. Relapsing fever Borrelia include both tick-borne (soft-shell, Ornithodoros spp.) and louse-borne species knowns to cause relapsing fever. A subgroup includes relapsing fever spirochetes carried by hard-shell ticks, including B. miyamotoi, an emerging pathogen. Despite bordering high-risk counties in Minnesota, little attention has been given to Lyme disease, B. burgdorferi, I. scapularis, or reservoirs in eastern North Dakota. Reports of B. burgdorferi and I. scapularis in North Dakota, however, prompted a more detailed examination. Through trapping Peromyscus and Myodes, five B. burgdorferi populations were obtained. We confirmed the presence of established, unique (nonclonal), and infectious B. burgdorferi populations in eastern North Dakota. Species of the B. burgdorferi s.l. complex possess two highly conserved hypothetical genes, bb0399 and bbb28, containing one of the most common protein motifs, ankyrin-repeat domains. The goal was to identify the function(s) of bb0399 and bbb28. Our hypothesis was BB0399 is an essential DNA binding protein and BBB28 is regulated by the Borrelia oxidative stress response regulator, BosR in response to an unknown stimuli. Exposing B. burgdorferi to tert-butyl hydroperoxide increased transcription of bbb28 but not bb0399. Several attempts to express recombinant BB0399 and BBB28 failed and the functions of bb0399 and bbb28 remain unknown. B. miyamotoi is an emerging pathogen vectored by the same Ixodes spp. carrying and transmitting B. burgdorferi. B. miyamotoi binds human factor H in vitro. C57BL/6J Rag1-/- mice infected with a Japanese strain of B. miyamotoi, FR64b, developed a chronic infection, while both 2-4 and 6-8 week-old wild-type C3H/HeN groups cleared B. miyamotoi. B. miyamotoi FR64b, normally vectored by I. persulcatus, was acquired by North American I. scapularis and maintained B. miyamotoi throughout the molting process from larvae to nymph, suggesting unlike other relapsing fever Borrelia, B. miyamotoi is not vector specific.

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