Identification of environmental and genetic factors affecting the survival of Legionella pneumophila in water.

我的研究计划的长期目标是了解水传播病原体在水环境中生存及其传播给人类宿主的环境和遗传因素。嗜肺军团菌是一种用于毒性机制和水媒病原体研究的水媒病原体模型，将用于本研究项目。嗜肺乳杆菌是军团病的病原体，军团病是社区获得性和医院感染性肺炎的重要病因，病死率高达50%。嗜肺乳杆菌通过吸入来自人造水系统（如淋浴和屋顶空调设备）的受污染水滴而传播。目前还没有深入了解影响嗜肺乳杆菌或其他水传播病原体在复杂的水微观环境中长期生存的全球参数，例如在受污染的水系统中发现的那些。我建议使用一种简化的方法，将系统简化到其基本组成部分，然后复制系统的复杂性将一步一步地增加。我未来五年的短期目标是确定和表征纯水系统中生存能力的基因，并表征一些环境因素对水中生存能力和毒性潜力的影响。这些研究结果的整合将提供一个影响嗜肺乳杆菌生存和传播到哺乳动物宿主的遗传和环境因素的全局观点，这些发现也应该适用于其他水传播病原体。这可能为控制人造水系统内细菌病原体的复制和防止传播给人类提供新的策略。这项研究计划将允许每年培训至少四名高素质人员，学习有关细菌病原体存在的尖端分子技术和水安全。

The long-term goal of my research program is to understand the environmental and genetic factors underlying the survival of water-borne pathogens in the water environment and their transmission to the human host. Legionella pneumophila, a model water-borne pathogen for the study of virulence mechanisms and water-borne pathogens, will be used for this research program. L. pneumophila is the causative agent of Legionnaires' disease, an important cause of community-acquired and nosocomial pneumonia with a high case-fatality rate approaching 50%. L. pneumophila is transmitted by inhalation of contaminated water droplets originating from human made water systems, such as showers and roof-top air-conditioning units. There is currently no insight into the global parameters affecting long-term survival of L. pneumophila or other water-borne pathogen in complex water microcosms, such as the ones found in contaminated water systems. I am proposing to use a reductionist approach in which the system will be reduced to its fundamental components and then the complexity of replicate systems will be increased one step at a time. My short-term objectives for the next five years are to identify and characterize genes underlying survivability in a pure water system and to characterize the effects of some environmental factors on the survivability in water and virulence potential. Integration of these findings should provide a global view of the genetic and environmental factors influencing L. pneumophila survival and transmission to mammalian hosts, and these findings should be applicable to other water-borne pathogens as well. This could provide new strategies to control the replication of bacterial pathogens inside man-made water systems and to prevent transmission to humans. This research program will allow the training of at least four highly qualified personnel per year in cutting-edge molecular techniques and water safety with regards to the presence of bacterial pathogens.