Biochemistry and Function of a Novel Bacterial Photosensory Two-Component System

描述（由申请人提供）：水传播微生物感染是一个重大的公共卫生问题，特别是在卫生设施不足的发展中国家。根据世界卫生组织的统计，每年发生超过130 000例霍乱（霍乱弧菌）和1 700万例伤寒（伤寒沙门氏菌）。值得注意的是，这些和其他致病微生物可以在天然水库和人体内茁壮成长。细菌在如此不同的环境中生存需要强大的感觉系统，可以快速调节细胞生理学。这种应用程序的重点是一种新的环境感觉系统的模型淡水细菌，新月柄杆菌的分子，遗传和生化特性。柄杆菌通常不是致病性的，但具有适应从蒸馏水到废水的各种水生环境的能力。除了作为自由生活的细胞存在外，柄杆菌还可以进入称为生物膜的多细胞发育状态。控制细菌生理和发育转变的细胞信号传导网络主要使用由组氨酸蛋白激酶及其同源反应调节蛋白组成的双组分信号转导系统。我们有证据表明C。crescentus包含由lovK和lovR基因编码的双组分信号系统，其检测光并调节细胞附着，这是生物膜发育的必要步骤。具体地，lovK编码光响应性组氨酸激酶，lovR基因编码单结构域响应调节剂。在人类和植物病原体中发现了相关的光传感器激酶，例如羊种布鲁氏菌、假单胞菌和野油菜黄单胞菌。光是一种无处不在的环境信号，可以作为细胞是在宿主生物体内部还是外部的代理。因此，光可能是一个重要的信号调节生物膜的形成和致病性在选择的细菌物种。柄杆菌是一个很好的模型系统，其中评估光和双组分信号在生物膜发育中的功能作用，因为有丰富的分子，遗传和基因组工具可用。公共卫生相关性I将确定光的质量和数量对细胞附着调节的影响，并确定柄杆菌中LovK/LovR信号通路的下游基因。通过这项工作，我们将更好地了解LovK/LovR双组分系统和无处不在的环境信号阳光在细菌生理和发育调节中的作用。

DESCRIPTION (provided by applicant): Waterborne microbial infection is a significant public health concern, particularly in developing countries where sanitation facilities are inadequate. According to the World Health Organization, over 130,000 cases of cholera (Vibrio cholerae) and 17 million cases of Typhoid fever (Salmonella typhi) occur annually. It is remarkable that these and other disease-causing microbes can thrive both in natural aquatic reservoirs and inside the human body. Bacterial survival across such varied environments requires robust sensory systems that can rapidly modulate cell physiology. This application focuses on the molecular, genetic, and biochemical characterization of a novel environmental sensory system in the model freshwater bacterium, Caulobacter crescentus. Caulobacter are not typically pathogenic, but have the ability to adapt to diverse aquatic environments ranging from distilled water to wastewater. In addition to existing as free-living cells, Caulobacter can also enter a multicellular developmental state known as a biofilm. The cellular signaling networks that control physiological and developmental transitions in bacteria largely use two-component signal transduction systems, consisting of histidine protein kinases and their cognate response regulator proteins. We have evidence that C. crescentus contains a two-component signaling system, encoded by the lovK and lovR genes, that detects light and regulates cellular attachment, a necessary step in biofilm development. Specifically, lovK encodes a photoresponsive histidine kinase and the lovR gene encodes a single-domain response regulator. Related photosensor kinases are found in human and plant pathogens such as Brucella melitensis, Pseudomonas syringae, and Xanthomonas campestris. Light is a ubiquitous environmental signal that can act as a proxy for whether a cell is inside or outside a host organism. Thus, light may be an important signal regulating biofilm formation and pathogenicity in select bacterial species. Caulobacter is an excellent model system in which to assess the functional role of light and two-component signaling in biofilm development because there are abundant molecular, genetic, and genomic tools available. Public Health Relevance I will determine the effects of light quality and quantity on the regulation of cellular attachment and define downstream genes in the LovK/LovR signaling pathway in Caulobacter. Through this work we will gain a better understanding of the role the LovK/LovR two-component system and the ubiquitous environmental signal, sunlight, in the regulation of bacterial physiology and development.