The intracellular bacteria Legionella pneumophila encodes a type IV secretion system (T4SS) that injects effector proteins into macrophages in order to establish and replicate within the Legionella-containing vacuole (LCV). Once generated, the LCV interacts with mitochondria through unclear mechanisms. We show that Legionella uses both T4SS-independent and T4SS-dependent mechanisms to respectively interact with mitochondria and induce mitochondrial fragmentation that ultimately alters mitochondrial metabolism. The T4SS effector MitF, a Ran GTPase activator, is required for fission of the mitochondrial network. These effects of MitF occur through accumulation of mitochondrial DNM1L, a GTPase critical for fission. Furthermore mitochondrial respiration is abruptly halted in a T4SS-dependent manner, while T4SS-independent upregulation of cellular glycolysis remains elevated. Collectively, these alterations in mitochondrial dynamics promote a Warburg-like phenotype in macrophages that favors bacterial replication. Hence the rewiring of cellular bioenergetics to create a replication permissive niche in host cells is a virulence strategy of L. pneumophila.

细胞内细菌嗜肺军团杆菌编码IV型分泌系统（T4SS），该系统将效应蛋白注入巨噬细胞，以便在含军团菌的液泡（LCV）中建立并复制。一旦产生，LCV通过不清楚的机制与线粒体相互作用。我们证明军团菌使用独立于T4SS的机制和依赖于T4SS的机制分别与线粒体相互作用并诱导线粒体片段化，最终改变线粒体的代谢。T4SS效应子MitF是Ran GTPase激活剂，是线粒体网络裂变所必需的。MitF的这些作用是通过线粒体DNM1L（一种对裂变至关重要的GTP酶）的积累而发生的。此外，线粒体呼吸以T4SS依赖性方式突然停止，而T4SS依赖性细胞糖酵解的上调仍然升高。总的来说，线粒体动力学的这些改变促进了巨噬细胞中的沃伯格样表型，有利于细菌复制。因此，细胞生物能学的重新布线以在宿主细胞中创建复制允许的生态位是一种毒力策略。嗜肺乳杆菌。