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潜在的水传播病原体在水环境中的生存及其传播给人类宿主的环境和遗传因素。嗜肺军团菌是研究毒力机制和水媒病原体的模式水媒病原体，将用于本研究计划。L.嗜肺菌是军团菌病的病原体，军团菌病是社区获得性肺炎和医院获得性肺炎的重要原因，病死率高达50%。L.嗜肺性肺炎是透过吸入来自人造水系统（例如淋浴及天台冷气机）的受污染水滴而传播。目前还没有深入了解影响L长期生存的总体参数。在复杂的水微观世界中，例如在受污染的水系统中发现的病原体。我建议使用一种简化的方法，将系统简化为其基本组成部分，然后一步一步地增加复制系统的复杂性。我在未来五年的短期目标是确定和表征基因的生存能力在纯净水系统和一些环境因素的影响，在水中的生存能力和毒力潜力的特点。综合这些研究结果，应该提供一个遗传和环境因素的影响L。嗜肺菌的生存和传播给哺乳动物宿主，这些研究结果应该适用于其他水传播的病原体以及。这可以提供新的策略来控制人造水系统内细菌病原体的复制，并防止传播给人类。这项研究计划将允许每年至少培训四名高素质的人员，掌握尖端分子技术和关于细菌病原体存在的水安全。

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.