Structure and Function of the Salmonella type III secretion sorting platform

PROJECT SUMMARY Type III secretion systems (T3SSs) are widely distributed among important gram-negative pathogenic bacteria. These complex specialized machines have evolved to transfer multiple bacterial-effector proteins into host eukaryotic cells to modulate a variety of cellular functions and they are essential for pathogenicity. The central component of T3SSs is a multi-protein structure known as the “injectisome”. This structure is composed of the envelope embedded needle complex (NC), and a cytoplasmic sorting platform (SP) that selects the substrates and energizes the secretion process. This research project focuses on the structural and functional characterization of the sorting platform. Through a multidisciplinary approach involving bacterial genetics, biochemistry, super-resolution microscopy, cryo-EM and cryo-ET, we intend to investigate the sorting platform structure and function, and in particular, the mechanism by which client proteins are selected and sorted. These studies will provide insight into poorly understood aspects of T3SS function. Importantly, given the high degree of conservation of this machine in many important pathogenic bacteria, knowledge gained with these studies will contribute to the understanding of T3SS in general, and therefore, generate knowledge that could be leveraged in fighting bacterial pathogenesis.