Schell Ursula, Simon Sylvia, Hilbi Hubert
Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.
Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30/32, 8006, Zürich, Switzerland.
Curr Top Microbiol Immunol. 2016;397:161-81. doi: 10.1007/978-3-319-41171-2_8.
The Gram-negative bacterium Legionella pneumophila colonizes extracellular environmental niches and infects free-living protozoa. Upon inhalation into the human lung, the opportunistic pathogen grows in macrophages and causes a fulminant pneumonia termed Legionnaires' disease. L. pneumophila employs a biphasic life cycle, comprising a replicative, non-virulent, and a stationary, virulent form. In the latter phase, the pathogen produces a plethora of so-called effector proteins, which are injected into host cells, where they subvert pivotal processes and promote the formation of a distinct membrane-bound compartment, the Legionella-containing vacuole. In the stationary phase, the bacteria also produce a single monopolar flagellum and become motile. L. pneumophila flagellin is recognized by and triggers the host's NAIP5 (Birc1e)/NLRC4 (Ipaf) inflammasome, which leads to caspase-1 activation, pore formation, and pyroptosis. The production of L. pneumophila flagellin and pathogen-host interactions are controlled by a complex stationary phase regulatory network, detecting nutrient availability as well as the Legionella quorum sensing (Lqs) signaling compound LAI-1 (3-hydroxypentadecane-4-one). Thus, the small molecule LAI-1 coordinates L. pneumophila flagellin production and motility, inflammasome activation, and virulence.
革兰氏阴性菌嗜肺军团菌定殖于细胞外环境生态位并感染自由生活的原生动物。吸入人体肺部后，这种机会致病菌在巨噬细胞中生长并引发一种暴发性肺炎，称为军团病。嗜肺军团菌采用双相生命周期，包括复制性、无毒形式和静止、有毒形式。在后者阶段，病原体产生大量所谓的效应蛋白，这些蛋白被注入宿主细胞，在那里它们破坏关键过程并促进形成一个独特的膜结合区室，即含军团菌液泡。在静止期，细菌还产生单根单极鞭毛并变得具有运动性。嗜肺军团菌鞭毛蛋白被宿主的NAIP5（Birc1e）/NLRC4（Ipaf）炎性小体识别并触发，导致半胱天冬酶-1激活、孔形成和细胞焦亡。嗜肺军团菌鞭毛蛋白的产生以及病原体与宿主的相互作用由一个复杂的静止期调控网络控制，该网络检测营养物质的可用性以及军团菌群体感应（Lqs）信号化合物LAI-1（3-羟基十五烷-4-酮）。因此，小分子LAI-1协调嗜肺军团菌鞭毛蛋白的产生和运动性、炎性小体激活以及毒力。
