The Tail-Specific Protease Is Important for Legionella pneumophila To Survive Thermal Stress in Water and inside Amoebae.

() is an inhabitant of natural and human-made water systems, where it replicates within amoebae and ciliates and survives within biofilms. When -contaminated aerosols are breathed in, can enter the lungs and may infect human alveolar macrophages, causing severe pneumonia known as Legionnaires' disease. is often found in hot water distribution systems (HWDS), which are linked to nosocomial outbreaks. Heat treatment is used to disinfect HWDS and reduce the concentration of However, is often able to recolonize these water systems, indicating an efficient heat shock response. Tail-specific proteases (Tsp) are typically periplasmic proteases implicated in degrading aberrant proteins in the periplasm and important for surviving thermal stress. In Philadelphia-1, Tsp is encoded by the gene. In this paper, we show that Tsp is important for surviving thermal stress in water and for optimal infection of amoeba when a shift in temperature occurs during intracellular growth. We also demonstrate that Tsp is expressed in the postexponential phase but repressed in the exponential phase and that the -encoded small regulatory RNA Lpr17 shows the opposite expression, suggesting that it represses translation of In addition, our results show that is regulated by CpxR, a major regulator in , in an Lpr17-independent manner. Deletion of CpxR also reduced the ability of to survive heat shock. In conclusion, our study shows that Tsp is likely an important factor for the survival and growth of in water systems. is a major cause of nosocomial and community-acquired pneumonia. is found in water systems, including hot water distribution systems. Heat treatment is a method of disinfection often used to limit the presence of in such systems; however, the benefit is usually short term, as is able to quickly recolonize these systems. Presumably, responds efficiently to thermal stress, but so far, not much is known about the genes involved. In this paper, we show that the Tsp and the two-component system CpxRA are required for resistance to thermal stress when is free in water and when it is inside host cells. Our study identifies critical systems for the survival of in its natural environment under thermal stress.