Dissertation
The Role of Linear Plasmid 28-1 in the Pathogenesis of Infection by Borrelia Burgdorferi
Doctor of Philosophy (PhD), Washington State University
01/2015
Handle:
https://hdl.handle.net/2376/111178
Abstract
THE ROLE OF LINEAR PLASMID 28-1 IN THE PATHOGENESIS OF INFECTION BY BORRELIA BURGDORFERI
by Petronella R. Hove, Ph.D.
Washington State University
August 2015
Chair: Troy Bankhead
Borrelia burgdorferi (Bb) is the etiological agent of Lyme borreliosis that causes disease and persistent infection due its ability to successfully evade host immune defenses. Factors involved in disease pathogenesis, particularly arthritis and persistence, have not yet been fully elucidated. Evidence suggests that some of these factors may be coded for by genes on linear plasmid 28-1 (lp28-1).
Lp28-1 codes for the Arthritis related protein (Arp). Antisera to Arp has been shown to prevent or reduce arthritis in immunodeficient mice. To directly investigate the requirement for this lipoprotein in the pathogenesis of Lyme arthritis, a mutant lacking the arp locus was generated. Following infection of immunocompetent mice, results in chapter one show that arp is required for early onset joint inflammation characterized by tibiotarsal joint swelling during the first 6 weeks and reduced histopathology scores in the first 2 weeks of infection. This deletion also had an effect on spirochete load as mice infected with the mutant had a greater spirochete burden in joint tissues.
In chapter two, the role of lp28-1 in the regulation of Outer surface protein C (OspC) is determined. It has been reported that lp28-1 may harbor a putative regulator required for the down regulation of OspC, which may in turn affect persistent infection by Bb. Gene conversion at the vls locus on lp28-1 results in antigenic variation of VlsE, demonstrated to be essential for immune evasion and persistence by the Lyme disease pathogen. To determine whether lack of the vls locus alone explains the lp28-1- phenotype, or whether dynamic expression of other immunogenic surface protein(s) such as OspC play a role, mutants lacking specific regions of lp28-1 questioned as potentially involved in OspC regulation were generated. Results show that in vitro expression of OspC remained unchanged. Additionally, mutants were able to persist for 91 days following infection in mice, and ospC expression was not significantly altered during host infection. Findings from the two studies show that lp28-1 harbors a lipoprotein required for maximal joint swelling and that the vls locus is the sole genetic element on this plasmid responsible for persistence by Bb.
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Details
- Title
- The Role of Linear Plasmid 28-1 in the Pathogenesis of Infection by Borrelia Burgdorferi
- Creators
- Petronella Runyararo Hove
- Contributors
- Troy Bankhead (Advisor)Kelly Brayton (Committee Member)Donald Knowles (Committee Member)Terry McElwain (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 87
- Identifiers
- 99900581527901842
- Language
- English
- Resource Type
- Dissertation