Modulation of the Phagolysosome by Salmonella

Shortly after invading host cells, Salmonella resides in vacuoles that fuse with lysosomes. This process is subsequently inhibited, allowing for bacterial survival and replication. Earlier work from the Andrews laboratory showed that permeabilization of the phagosome by the SPI1 type three secretion systems (TTSS) triggers fusion of lysosomes with Salmonella-containing vacuoles shortly after bacterial entry. This process is inhibited in synaptotagmin Vll-deficient macrophages, leading to more vigorous bacterial growth. Synaptotagmin VII, a calcium sensor molecule present on the membrane of lysosomes, interacts with the lysosomal SNARE molecule VAMP7 and facilitates lysosomal fusion. <P> In this project we will test the hypothesis that Salmonella inhibits phagolysosomal fusion by translocating into the host cytosol effector molecules that inhibit the activity of Syt VII, VAMP7 and/or other host cell proteins that regulate phagosome-lysosome fusion.