Use of zebrafish to study innate immunity to Shigella in vivo. (360G-Wellcome-097411_Z_11_B)

Background: Several intracellular pathogens escape from phagosomes and reach the host cytosol where they can polymerize actin, leading to motility and cell-to-cell spread. However, only a small fraction of intracytosolic bacteria form actin tails, and a complete understanding of the molecular events restricting bacterial dissemination has not been obtained. Objectives: Using Shigella flexneri I will pursue the following aims: (1) To identify and characterize host and pathogen determinants un derlying the intracellular fate of cytosolic bacteria; (2) To investigate the role of discovered molecules and mechanisms in vivo using new experimental models of infection. Expected results: Completion of these objectives will provide insights into the mechanisms required for the control of infection by cytosolic host responses.