The Legionella pneumophila replication vacuole: making a cosy niche inside host cells

Abstract
Legionella pneumophila is a Gram-negative intracellular pathogen of both amoebae and humans that grows in lung macrophages. The intracellular replication strategy of this bacterium, which involves growth in a membrane-bound compartment called a vacuole, seems to be similar in all cell types in which it grows. A protein translocation apparatus that encodes more than 20 proteins, called Dot/Icm, is required for formation of the replication vacuole and intracellular growth. Proteins move through the apparatus across membranes in contact with the bacterium, and are thought to manipulate host cell proteins that are involved in host cell secretory traffic. Eighty five translocated protein substrates of Dot/Icm have been identified, but there are probably many more. The targets of several have been identified, and they include proteins that modulate the activation state of Arf1 and Rab1 and are involved in vesicle trafficking in host cells, as well as proteins that antagonize host cell death pathways. Mutations in single translocated substrates rarely result in strong defects in intracellular growth. This has led to the model that there is considerable functional redundancy among the substrates. A model is provided to attempt to explain how L. pneumophila acquired such a diverse set of translocated substrates.

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