Intravacuolar pathogens need to gradually expand their surrounding vacuole to accommodate the growing number of bacterial offspring during intracellular replication. Here we found that Legionella pneumophila controls vacuole expansion by fine-tuning the generation of lysophospholipids within the vacuolar membrane. Upon allosteric activation by binding to host ubiquitin, the type IVB (Dot/Icm) effector VpdC converts phospholipids into lysophospholipids which, at moderate concentrations, are known to promote membrane fusion but block it at elevated levels by generating excessive positive membrane curvature. Consequently, L. pneumophila overproducing VpdC were prevented from adequately expanding their surrounding membrane, trapping the replicating bacteria within spatially confined vacuoles and reducing their capability to proliferate intracellularly. Quantitative lipidomics confirmed a VpdC-dependent increase in several types of lysophospholipids during infection, and VpdC production in transiently transfected cells caused tubulation of organelle membranes as well as mitochondria fragmentation, processes that can be phenocopied by supplying cells with exogenous lysophospholipids. Together, these results demonstrate an important role for bacterial phospholipases in vacuolar expansion.

中文翻译：

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VpdC 是一种泛素激活的磷脂酶效应物，可在感染期间调节军团菌液泡扩张

液泡内病原体需要逐渐扩大其周围的液泡，以适应细胞内复制过程中越来越多的细菌后代。在这里我们发现嗜肺军团菌通过微调液泡膜内溶血磷脂的产生来控制液泡扩张。通过与宿主泛素结合进行变构激活后，IVB 型 (Dot/Icm) 效应子 VpdC 将磷脂转化为溶血磷脂，已知溶血磷脂在中等浓度下可促进膜融合，但在高水平时会通过产生过度的正膜曲率来阻断它。最后，嗜肺军团菌过度生产的 VpdC 被阻止充分扩展其周围的膜，将复制细菌困在空间受限的液泡内并降低它们在细胞内增殖的能力。定量脂质组学证实，在感染期间，几种类型的溶血磷脂依赖于 VpdC 增加，瞬时转染细胞中 VpdC 的产生导致细胞器膜的微管化以及线粒体断裂，这些过程可以通过为细胞提供外源性溶血磷脂来表型复制。总之，这些结果证明了细菌磷脂酶在液泡扩张中的重要作用。