Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis
Lyme disease is the most prevalent vector-borne disease in United States and is caused by the spirochete Borrelia burgdorferi. The disease is transmitted from an infected Ixodes scapularis tick to a mammalian host. B. burgdorferi is a highly motile organism and motility is provided by flagella that are enclosed by the outer membrane and thus are called periplasmic flagella. Chemotaxis, the cellular movement in response to a chemical gradient in external environments, empowers bacteria to approach and remain in beneficial environments or escape from noxious ones by modulating their swimming behaviors. Both motility and chemotaxis are reported to be crucial for migration of B. burgdorferi from the tick to the mammalian host, and persistent infection of mice. However, the knowledge of how the spirochete achieves complex swimming is limited. Moreover, the roles of most of the B. burgdorferi putative chemotaxis proteins are still elusive. B. burgdorferi contains multiple copies of chemotaxis genes (two cheA, three cheW, three cheY, two cheB, two cheR, cheX, and cheD), which make its chemotaxis system more complex than other chemotactic bacteria. In the first project of this dissertation, we determined the role of a putative chemotaxis gene cheD. Our experimental evidence indicates that CheD enhances chemotaxis CheX phosphatase activity, and modulated its infectivity in the mammalian hosts. Although CheD is important for infection in mice, it is not required for acquisition or transmission of spirochetes during mouse-tick-mouse infection cycle experiments. However, it has an effect on the survivability of spirochetes in the arthropod vectors. This is the first report of the role of cheD in the host tissue colonization in any pathogenic bacterium. Delineating the role of cheD in B. burgdorferi will provide insights into not only the chemotaxis pathway of this spirochete, but also its asymmetric swimming and infectious life cycle of the spirochete. Chemotaxis signal transduction systems control bacterial motility. Aside from the chemotaxis pathway, the architectural structure of the flagellar apparatus is also intimately intertwined with motility and the morphology of B. burgdorferi. Unlike other externally flagellated bacteria, spirochetes possess periplasmic flagella with a unique structural component called the collar. This unique component is located in the periplasmic space and is linked to the flagellar basal body. However, there are no reports regarding the gene(s) encoding for the collar or its function in any bacterium. In the second project of this dissertation, we have identified for the first time a gene, flbB, in any spirochete, and defined its function in motility, cell morphology, periplasmic flagella orientation, and assembly of other flagellar structures. We also demonstrated the mechanism shown as to how the organism tilts their periplasmic flagella toward the cell pole.
Moon, Kihwan. (August 2016). Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/6028.)
Moon, Kihwan. Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis. Doctoral Dissertation. East Carolina University, August 2016. The Scholarship. http://hdl.handle.net/10342/6028. September 21, 2020.
Moon, Kihwan, “Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis” (Doctoral Dissertation., East Carolina University, August 2016).
Moon, Kihwan. Motility and chemotaxis in the Lyme disease spirochete Borrelia burgdorferi : role in pathogenesis [Doctoral Dissertation]. Greenville, NC: East Carolina University; August 2016.
East Carolina University