Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Author ORCID Identifier
https://orcid.org/0000-0001-5899-8529
AccessType
Campus-Only Access for One (1) Year
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Microbiology
Year Degree Awarded
2023
Month Degree Awarded
May
First Advisor
Stephen M. Rich
Subject Categories
Bacteriology | Microbiology | Molecular Biology | Pathogenic Microbiology
Abstract
The research presented herein is multifaceted and focuses on B. burgdorferi, a tickborne bacterium and causative agent of Lyme disease. First, we tested the efficacy of a known drug, tranexamic acid (TXA), against B. burgdorferi in vivo. We reasoned that TXA may impact B. burgdorferi infectivity, since TXA competitively binds the host molecule plasminogen, which B. burgdorferi appropriates for more efficient dissemination through a feeding tick and host. In experiments using needle- and tick-inoculated mice, no difference in B. burgdorferi infectivity was found between treated and control mice. The administration of TXA to impact B. burgdorferi in vivo was a novel approach but due to its inefficacy is unlikely to be an option in the management of Lyme disease. Second, we optimized and developed a B. burgdorferi outer surface protein C (ospC) genotyping assay. In the northeastern United States, there are at least 19 ospC genotypes, and reliable detection of these genotypes is valuable for basic research and public health. Our assay was validated by comparing results obtained from our method against results from an established ospC genotyping method. We believe our assay is a valuable addition to the field and can be used by other researchers for efficient characterization of B. burgdorferi ospC genotypes. Third, we determined whether resistance to serum-mediated killing is a factor contributing to the ability of specific B. burgdorferi strains, as defined by their ospC genotype, to infect humans. The majority of disseminated Lyme disease cases are caused by only a subset of the B. burgdorferi strains and are referred to as the human invasive strains. Since the killing activity of host serum is a powerful determinant of whether Borrelia spirochetes can infect a host, we determined whether the human invasive strains are differentially resistant to human serum. No difference in human serum-mediated killing was found between invasive and noninvasive strains, suggesting some other factor(s) must be driving this association. In parallel with this research, we also determined that strains were universally killed by white-tailed deer serum which provides a likely mechanism explaining the poor reservoir competence of this species.
DOI
https://doi.org/10.7275/34992612
Recommended Citation
Pearson, Patrick, "BORRELIA BURGDORFERI: DRUG TESTING, ASSAY DEVELOPMENT, AND THE ROLE OF SERUM-MEDIATED KILLING IN THE INFECTIVITY PHENOTYPE" (2023). Doctoral Dissertations. 2843.
https://doi.org/10.7275/34992612
https://scholarworks.umass.edu/dissertations_2/2843