Borrelia burgdorferi, lp36, bbk46, in vivo expression technology, gene expression, virulence factor
The spirochete Borrelia burgdorferi is the etiologic agent of Lyme disease. This pathogen has a complex enzootic life cycle that involves passage between the tick vector (Ixodes scapularis) and various vertebrate hosts with humans being inadvertent hosts. There is a pressing need to study the genetic aspects of the B. burgdorferi infectious cycle and particularly spirochete genes involved in mammalian infectivity so as to develop novel therapeutic and diagnostic strategies to combat Lyme disease. The B. burgdorferi genome is fragmented and comprised of a single 900 kb linear chromosome and multiple linear and circular plasmids. It has been observed that plasmids are lost during serial passage and manipulation in vitro and the loss of some of the plasmids has been shown to be related to the loss of infectivity and persistence in the host. One such plasmid is linear plasmid 36 (lp36). lp36 is approximately 36kb in size and carries 56 putative open reading frames a majority of which have no predicted function. B. burgdorferi lacking lp36 show no deficiency in survival in ticks; however, these mutant spirochetes are highly attenuated for mammalian infectivity. The genetic components of this plasmid that contribute to its function in mammalian infectivity have yet to be clearly defined. Using an in vivo expression technology (IVET) based genetic screen the lp36- encoded gene bbk46 was identified as a candidate B. burgdorferi gene that is expressed during mammalian infection. Herein we present evidence that bbk46 is required for B. burgdorferi persistent infection of immunocompetent mice. Our data iii support a molecular model of immune evasion by which bbk46 functions as an RNA to regulate expression of the antigenic variation protein VlsE. These data represent the first demonstration of a regulatory mechanism critical for controlling vlsE gene expression. Moreover these findings further define the critical role of linear plasmid 36 in Borrelia burgdorferi pathogenesis.
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Doctor of Philosophy (Ph.D.)
College of Medicine
Molecular Biology and Microbiology
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Dissertations, Academic -- Medicine, Medicine -- Dissertations, Academic
Choudhury, Tisha, "Delineating Key Genetic Components On Linear Plasmid 36 That Contribute To Its Essential Role In Borrelia Burgdorferi Mammalian Infectivity." (2013). Electronic Theses and Dissertations, 2004-2019. 2996.