The gram-negative bacterial pathogen creates a novel organelle inside of eukaryotic host cells that supports intracellular replication. The –containing vacuole evades fusion with lysosomes and interacts intimately with the host endoplasmic reticulum (ER). Although the natural hosts for are free-living protozoa that reside in freshwater environments, the mechanisms that enable this pathogen to replicate intracellularly also function when mammalian macrophages phagocytose aerosolized bacteria, and infection of humans by can result in a severe pneumonia called Legionnaires' disease. A bacterial type IVB secretion system called Dot/Icm is essential for intracellular replication of . The Dot/Icm apparatus delivers over 300 different bacterial proteins into host cells during infection. These bacterial proteins have biochemical activities that target evolutionarily conserved host factors that control membrane transport processes, which results in the formation of the ER-derived vacuole that supports replication. This review highlights research discoveries that have defined interactions between vacuoles containing and the host ER. These studies reveal how creates a vacuole that supports intracellular replication by subverting host proteins that control biogenesis and fusion of early secretory vesicles that exit the ER and host proteins that regulate the shape and dynamics of the ER. In addition to recruiting ER-derived membranes for biogenesis of the vacuole in which replicates, these studies have revealed that this pathogen has a remarkable ability to interfere with the host's cellular process of autophagy, which is an ancient cell autonomous defense pathway that utilizes ER-derived membranes to target intracellular pathogens for destruction. Thus, this intracellular pathogen has evolved multiple mechanisms to control membrane transport processes that center on the involvement of the host ER.


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