Pore-forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth

Bacterial pathogens often subvert eukaryotic cellular processes in order to establish a replicative niche and evade host immunity. Inhibition of phago some lysosome fusion is a strategy used by several Intracellular bacteria t hat grow within mammalian cells, it was shown recently that Legionella pneu mophiia possesses a cytolytic activity that results from the insertion of p ores in the macrophage membrane upon contact, and that this activity requir es the dot/icm gene products, which are necessary for intracellular growth and phagosome trafficking. Other bacteria that inhibit phagosome lysosome f usion, such as Mycobacterium tuberculosis, demonstrate similar cytolytic ac tivities, which suggests that formation of pores in the phagosome membrane may account for the defects observed in phagosome trafficking. In this stud y, we identify a new class of L, pneumophila mutant that retains the pore-f orming activity found in virulent bacteria, but is defective in phagosome l ysosome fusion inhibition and intracellular growth. These data indicate tha t cytolytic activity is not sufficient for L. pneumophila-induced alteratio ns in phagosome trafficking. Rather, the pore may be a vehicle that facilit ates delivery of bacterial-derived effector molecules to the host cell cyto plasm.