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

描述（由申请人提供）：水传播的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。据世界卫生组织统计，每年有超过13万例霍乱（霍乱弧菌）和1700万例伤寒（伤寒沙门氏菌）。值得注意的是，这些和其他致病微生物既可以在天然水生水库中繁殖，也可以在人体内繁殖。细菌在如此多变的环境中生存需要能够快速调节细胞生理的强大的感觉系统。本应用程序的重点是分子，遗传和生化表征的一种新型环境感觉系统的模式淡水细菌，新月形茎杆菌。茎状杆菌通常不具有致病性，但具有适应从蒸馏水到废水等各种水生环境的能力。除了作为自由活细胞存在外，茎状杆菌还可以进入一种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网络主要使用双组分信号转导系统，由组氨酸蛋白激酶及其同源反应调节蛋白组成。我们有证据表明，月牙草含有一个由lovK和lovR基因编码的双组分信号系统，该系统检测光线并调节细胞附着，这是生物膜发育的必要步骤。具体来说，lovK基因编码光反应性组氨酸激酶，而lovR基因编码单结构域反应调节因子。相关的光敏激酶存在于人类和植物病原体中，如布鲁氏菌、丁香假单胞菌和油菜黄单胞菌。光是一种无处不在的环境信号，可以作为细胞是在宿主体内还是体外的代理。因此，光可能是调控生物膜形成和致病性的重要信号。Caulobacter是一个很好的模型系统，用于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。我将确定光的质量和数量对茎状杆菌细胞附着调控的影响，并确定在LovK/LovR信号通路中的下游基因。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.