Doctor of Philosophy (PhD)
Veterinary Medical Sciences - Pathobiological Sciences
The outer surface lipoprotein (osp) layer forms an interface between the internal and the external environment of the Lyme disease spirochete, Borrelia burgdorferi. The homeostatic maintenance of the osp layer effectuates adaptation of B. burgdorferi as it gets transmitted from the tick vector to a mammalian host and vice-versa. However, the regulation of the outer surface lipoproteins (osps) is still a conundrum for borrelia scientists. Part of this dissertation inquires about the homeostatic maintenance of the osp layer. We found that the deletion of the dominantly expressed tick phase osp, OspA, induces expression of two other osps. OspD, and BBJ41. Also, increased expression of OspC was seen in borrelia mutants lacking OspA, OspD, and BBJ41. These results suggest constant osp layer maintenance, irrespective of the presence or the absence of the dominant Osps, like OspA and OspC. Furthermore, our conclusive electron microscopic study demonstrates that the overall density of the osp layer remains identical in wild type and mutant B. burgdorferi, lacking either several osps or the dominantly expressed OspA. OspA is abundantly expressed on the borrelial surface as it persists in an unfed tick. A blood meal causes rapid downregulation of OspA as B.burgdorferi prepares to infect the mammalian host. The downregulation of OspA is speculated to be regulated by an unknown repressor protein. The remaining part of this dissertation pertains to the investigation of this unknown repressor protein for ospA. The borrelia oxidative stress regulator protein, BosR, has been attributed with an indirect role in OspA downregulation. However, due to its homolgy with a family of transcriptional repressors, BosR is more likely to cause direct repression of OspA. Therefore, we investigated the direct interaction of BosR and the ospA regulatory region. The DNA binding experiments demonstrated that borrelia oxidative stress regulator, BosR, binds directly to the cisI and cisII regulatory regions of ospA promoter. Thus, conclusively, BosR acts as a repressor protein which causes OspA downregulation in B. burgdorferi.
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Dadhwal, Poonam, "Outer Surface Lipoprotein Layer Homeostasis and Gene Regulation in Borrelia burgdorferi" (2014). LSU Doctoral Dissertations. 2540.
Liang, Fang Ting