Defining virulence factor functions using minimal pathogen genomes

The project will investigate the fundamental mechanism of bacterial division in conjunction with vacuolar scission in Salmonella enterica. It will use genetically minimal pathogenic strains to determine how a small network of SPI-2 T3SS effector proteins coordinate SCV membrane scission and bacterial division within host cells. This involves determining the location and host substrates of effector proteins at the SCV membrane using single cell particle tracking and live cell imaging (Aim 1), investigating molecular mechanisms of individual effector proteins targeting a novel Rab-family GTPase defense system (Aim 2), and testing resulting cellular and biochemical theories in murine models of systemic disease to evaluate effector protein functions at single cell resolution (Aim 3). The ultimate goal is to predict new mechanisms of action for understudied Salmonella effector proteins and provide insight into the structural-based evolutionary progression of related pathogen groups, potentially informing new drug development.