Borrelia burdorferi Ebfc regulon

描述（由申请方提供）：宿主的成功感染需要入侵病原体控制其毒力决定因子的产生。感染原必须感知其环境，然后通过增加适当因子的产生和抑制不必要因子的产生来做出反应。这些特征对于媒介传播的病原体尤其重要，它们不仅必须有效地感染两种截然不同的宿主类型，而且还必须在宿主之间来回传播。破译病原体用来控制感染相关蛋白质产生的调控途径将为这些生物体的感染性提供重要的见解。此外，调节途径是开发新的预防性和治疗性疗法的有吸引力的候选者。我们发现莱姆病螺旋体，伯氏疏螺旋体，利用一种名为EbfC的位点特异性DNA结合蛋白来调节超过50种不同基因（>5%的基因组）的表达。EbfC调节子包括已知在细菌感染周期中差异表达的基因，并且与哺乳动物感染相关。我们假设，EbfC是关键的细菌基因表达的全局调节，和EbfC调节子的失调将防止有效的哺乳动物感染。为了解决这一假设，我们将严格检查EBFC对疏螺旋体哺乳动物蜱感染周期各个方面的影响 绝大多数其他细菌物种，包括许多病原体，编码EbfC的同源物。几乎没有人知道这些其他细菌的同源物，所以我们的研究将影响几乎整个域真细菌。因此，我们继续的研究将集中精力生产改进的预防和治疗方法，不仅用于莱姆病，而且用于许多其他重要的人类传染病。

DESCRIPTION (provided by applicant): Successful infection of a host requires that the invading pathogen control production of its virulence determinants. The infectious agent must sense its environment, then respond by increasing production of appropriate factors and repressing production of unnecessary ones. These features are especially critical for vector-borne pathogens, which must not only efficiently infect two extremely different host types, but also be transmitted back and forth between hosts. Deciphering the regulatory pathways used by pathogens to control production of infection-associated proteins will provide significant insight into the infectious nature of those organisms. Moreover, regulatory pathways are attractive candidates for development of novel preventative and curative therapies. We discovered that the Lyme disease spirochete, Borrelia burgdorferi, utilizes a site-specific DNA-binding protein named EbfC to regulate expression of over 50 different genes (>5% of its genome). The EbfC regulon includes genes known to be differentially expressed during the bacteria's infectious cycle, and to be associated with mammalian infection. We hypothesize that EbfC is critical for global regulation of bacterial gene expression, and that dysregulation of the EbfC regulon will prevent efficient mammalian infection. To address that hypothesis, we will critically examine the effects of EbfC on all aspects of the borrelial mammal-tick infectious cycle The vast majority of other bacteria species, including many pathogens, encode homologs of EbfC. Almost nothing is known about those other bacteria's homologs, so our studies will have impacts upon almost the entire domain Eubacteria. Thus, our continued studies will focus efforts toward production of improved preventative and curative therapies for not only Lyme disease, but also many other significant human infectious diseases.