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

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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.