Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth

Legionella pneumophila is a bacterial pathogen that can enter the human lun g and grow inside alveolar macrophages, To grow within phagocytic host cell s, the bacteria must create a specialized organelle that restricts fusion w ith lysosomes, Biogenesis of this replicative organelle is controlled by 24 dot and icm genes, which encode a type iv-related transport apparatus. To understand how this transporter functions, isogenic L. pneumophila dot and icm mutants were characterized, and three distinct phenotypic categories we re identified. Our data show that, in addition to genes that encode the cor e Dot/Icm transport apparatus, subsets of genes are required for pore forma tion and modulation of phagosome trafficking. To understand activities requ ired for virulence at a molecular level, we investigated protein-protein in teractions, Specific interactions between different Icm proteins were detec ted by yeast two-hybrid and gel overlay analysis. These data support a mode l in which the IcmQ-IcmR complex regulates the formation of a translocation channel that delivers proteins into host cells, and the IcmS-IcmW complex is required for export of virulence determinants that modulate phagosome tr afficking.