Type of Document	Dissertation
Author	Seemanapalli, Sunita V
Author's Email Address	sseema1@tigers.lsu.edu
URN	etd-02202010-133406
Title	OspC in the Pathogenesis of Borrelia burgdorferi
Degree	Doctor of Philosophy (Ph.D.)
Department	Pathobiological Sciences (Veterinary Medical Sciences)
Advisory Committee	Advisor Name Title Liang, Fang-Ting Committee Chair Macaluso, Kevin Committee Co-Chair Elzer, Philip H. Committee Member Kousoulas, Konstantin G. Committee Member Schowalter, Timothy D. Dean's Representative
Keywords	Vector-borne disease Spirochetes
Date of Defense	2010-01-13
Availability	unrestricted
Abstract Lyme disease is a multisystem disorder caused by the tick vector Borrelia burgdorferi. During its life cycle between the tick vector and the mammalian host, Borrelia up- and down-regulates the expression of its surface lipoproteins. Of its many surface lipoproteins, the Outer surface protein C (OspC) is crucial for initial mammalian infection. OspC has a common role shared with other lipoproteins of protection against host innate defences and a unique function in facilitating the dissemination of B. burgdorferi in the murine host. The structure of OspC was solved in 2001 and the lipoprotein was found to be predominantly alpha-helical with 5 alpha helices and 2 beta sheets interconnected by 6 loops, and an N- and C-terminus. Not much is known as to how the OspC structure relates to the function of the lipoprotein and/or possible regulation. The up-and down-regulation of OspC is achieved by the rpoS alternative sigma factor and by an unidentified repressor, respectively. Several truncated versions of OspC were tested in an OspC-deficient background to better understand the role of the amino acid sequences deleted. Structural deletions of 5 to 8-AA made within the OspC core, resulted in loss of infectivity. Longer deletions of 10- and 13 AA towards the N- and C-terminus of OspC, respectively, also resulted in loss of infectivity. Interestingly, a deletion of only 5-AA of the N-terminus of OspC did not affect the role of OspC in evasion but caused inefficient dissemination of B. burgdorferi in SCID mice. Interestingly, whereas the deletion of N-terminus 5-AA of OspC resulted in upregulation, a deletion of 6- and 9-AA of the C-terminus of OspC resulted in downregulation of ospC mRNA in joints, indicating that OspC may be involved in self-regulation. This hypothesis was confirmed by the use of monoclonal antibody treatment. Deletion of 6-AA of the C-terminus of OspC resulted in lower spirochete burdens in heart and joint, whereas deletion of 9-AA resulted in higher spirochete burden in skin, indicating the tissue-dependent effects resulting from the deletion of the C-terminal sequence. Taken together, these results indicate that OspC is involved in the pathogenesis of B. burgdorferi.
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