Borrelia burdorferi Ebfc regulon

描述(申请人提供)：寄主的成功感染要求入侵病原体控制其毒力决定因素的产生。感染性病原体必须感知其环境，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。这些特征对于病媒传播的病原体尤其关键，因为病原体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产生的调控途径，将为了解这些生物的感染性提供重要的洞察力。此外，调节通路是开发新的预防和治疗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50多个不同基因的表达(占其基因组的5%)。EbfC调节子包括已知在细菌感染周期中差异表达的基因，并与哺乳动物感染有关。我们假设EbfC对于细菌基因表达的全球调控至关重要，EbfC调节子的失调将阻止有效的哺乳动物感染。为了解决这一假设，我们将批判性地检查Ebfc对丝状哺乳动物-壁虱感染循环各个方面的影响。 绝大多数其他细菌物种，包括许多病原体，编码EbfC的同源物。几乎对这些其他细菌的同源物一无所知，所以我们的研究将对几乎整个领域的真细菌产生影响。因此，我们继续的研究将集中精力，不仅针对莱姆病，而且针对许多其他重要的人类传染病，改进预防和治疗方法。

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.