Understanding the mechanisms employed by Legionella to survive in diverse environments

在水和潮湿的土壤环境中，单细胞生物（称为原生动物）以细菌为食物。一种细菌，军团菌，是原生动物的寄生虫，当摄入时，使用原生动物宿主细胞作为其生命周期的食物来源。军团菌的生命周期是独特的，因为它在两种细菌形式之间交替：复制形式（RF）和囊肿样形式（CLF）。当食物丰富时，RF会主动复制自己，当细菌感觉到食物变得稀缺时，RF会分化成具有强化细胞壁的CLF，以确保在环境中生存。消耗的原生动物宿主细胞爆裂，将CLF释放到环境中，在那里它们将被觅食的原生动物摄取，重复生命周期。CLF比RF更具传染性，目前认为，当CLF在水滴中雾化并被免疫功能低下的人无意中吸入时，它们可引起称为军团病（LD）的呼吸道感染。我使用各种分子生物学工具，在互补的研究方法来阐明宿主和军团菌之间的相互作用。特别是，这项研究的目的是调查控制原生动物CLF形成的调节机制，其结果将导致改善水质的策略。军团菌的宿主包括天然和人造淡水系统，最近发现军团菌可以在通常存在于潮湿土壤环境中的自由生活的线虫中经历其生命周期。这项研究将进一步研究线虫中的军团菌生命周期，以调查线虫是否可以在土壤中保留和分散军团菌。如果是这种情况，那么自由生活的线虫可能既是自然环境中军团菌的储存者，也是军团菌的放大者。这种生态因素以前没有考虑在军团菌病的病因学，从而调查线虫宿主的作用将有一个巨大的影响，目前的理解军团菌的调节机制，以适应和生存在不同的环境。

In water and moist soil environments, unicellular organisms (termed protozoa) eat bacteria for food. One type of bacterium, Legionella, is a parasite of protozoa and when ingested, uses the protozoan host cell as a food source for its lifecycle. The Legionella lifecycle is unique because it alternates between two bacterial forms: the replicative form (RF) and the cyst-like form (CLF). When food is abundant, RFs actively replicate themselves and when the bacteria sense that food is becoming scarce, the RFs differentiate into CLFs featuring fortified cell walls to ensure survival in the environment. The spent protozoan host cell bursts open releasing the CLFs into the environment where they will be ingested by foraging protozoa repeating the life-cycle. The CLFs are much more infectious than the RFs, and it is currently believed that when CLFs are aerosolized in water droplets and inadvertently inhaled by immunocompromised humans, they can cause a respiratory infection called Legionnaires' disease (LD). I use a diverse range of molecular biological tools in complementary research approaches to elucidate the interactions between the host and Legionella bacteria. In particular, this research is intended to investigate the regulatory mechanisms controlling CLF formation in protozoa, and the results will lead to improved water quality strategies. Reservoirs of Legionella bacteria include natural and man-made freshwater systems, and recently it was discovered that Legionella bacteria can undergo their lifecycle in free-living nematodes normally present in moist soil environments. This research will further examine the Legionella life-cycle in nematodes to investigate whether nematodes can retain and disperse Legionella bacteria within the soil. If this is the case, then free-living nematodes may serve both as reservoir and an amplifier of Legionella in the natural environment. This ecological factor was not previously considered in the etiology of Legionnaire's disease, and thereby investigating the role of the nematode host will have a dramatic impact on the current understanding of the regulatory mechanisms used by Legionella bacteria to adapt and survive in diverse environments.