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。军团菌是一种原生动物的寄生虫，当被摄入时，它将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）。当食物充足时，RFs积极地自我复制，当细菌感觉到食物变得稀缺时，RFs分化成具有强化细胞壁的CLFs，以确保在环境中生存。耗尽的原生动物宿主细胞破裂，释放出clf到环境中，在那里它们将被觅食的原生动物摄入，重复生命周期。clf的传染性比rf强得多，目前认为，当clf以水滴雾化并被免疫功能低下的人无意中吸入时，它们会引起一种称为军团病（LD）的呼吸道感染。我使用不同范围的分子生物学工具在互补的研究方法来阐明宿主和军团菌细菌之间的相互作用。本研究旨在探讨原生动物CLF形成的调控机制，为改善水质策略提供依据。军团菌的宿主包括天然和人工淡水系统，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线虫中度过其生命周期。本研究将进一步研究线虫体内军团菌的生命周期，探讨线虫是否能够在土壤中保留和分散军团菌。如果是这样的话，那么在自然环境中，自由生活的线虫可能既是军团菌的储存库，也是军团菌的扩大器。这一生态因素在军团病的病因学中没有被考虑到，因此研究线虫宿主的作用将对目前对军团菌在不同环境中适应和生存的调节机制的理解产生巨大影响。

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.