Evolution of the Arsenal of Legionella pneumophila Effectors To Modulate Protist Hosts.

Within the human host, replicates within alveolar macrophages, leading to pneumonia. However, is an aquatic generalist pathogen that replicates within a wide variety of protist hosts, including amoebozoa, percolozoa, and ciliophora. The intracellular lifestyles of within the two evolutionarily distant hosts macrophages and protists are remarkably similar. Coevolution with numerous protist hosts has shaped plasticity of the genome of , which harbors numerous proteins encoded by genes acquired from primitive eukaryotic hosts through interkingdom horizontal gene transfer. The Dot/Icm type IVb translocation system translocates ∼6,000 effectors among species and >320 effector proteins in into host cells to modulate a plethora of cellular processes to create proliferative niches. Since many of the effectors have likely evolved to modulate cellular processes of primitive eukaryotic hosts, it is not surprising that most of the effectors do not contribute to intracellular growth within human macrophages. Some of the effectors may modulate highly conserved eukaryotic processes, while others may target protist-specific processes that are absent in mammals. The lack of studies to determine the role of the effectors in adaptation of to various protists has hampered the progress to determine the function of most of these effectors, which are routinely studied in mouse or human macrophages. Since many protists restrict , utilization of such hosts can also be instrumental in deciphering the mechanisms of failure of to overcome restriction of certain protist hosts. Here, we review the interaction of with its permissive and restrictive protist environmental hosts and outline the accomplishments as well as gaps in our knowledge of -protist host interaction and 's evolution to become a human pathogen.