The environmental bacterium Legionella pneumophila is the causative agent of a severe pneumonia termed “Legionnaires’ disease”. L. pneumophila is a strictly aerobic, facultative intracellular pathogen, which grows in protozoa and macrophages within a unique membrane-bound compartment, the “Legionella-containing vacuole” (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates more than 300 different “effector” proteins into host cells, where they subvert pivotal processes. LCVs restrict fusion with lysosomes and intimately interact with the endoplasmic reticulum (ER) through membrane contact sites. L. pneumophila also promotes host cell interactions through an α-hydroxyketone molecule termed Legionella autoinducer-1 (LAI-1).

A hallmark of LCV formation is the phosphoinositide lipid conversion from endosomal PtdIns(3)P to secretory PtdIns(4)P. Proteomics of purified, intact LCVs revealed host factors presumably involved in LCV formation, including small and large GTPases. Indeed, LCV formation implicates effectors subverting the small GTPase Ran and large GTPases, such as atlastin 3 (Atl3)/Sey1 and dynamin-related protein 1 (Drp1), which are involved in ER, lipid droplet (LD) and mitochondria dynamics. Moreover, the signaling molecule LAI-1 also localizes to the LCV membrane. Recent progress in our understanding of LCV formation and LAI-1-dependent inter-kingdom signaling will be discussed.