Dynamic modification of microtubule-dependent transport by Salmonella effector proteins
Zusammenfassung der Projektergebnisse
Intracellular "Salmonella enterica" induce the massive remodeling of the endosomal system in infected host cells. The most dramatic consequence of this interference is the induction of extensive tubular aggregations of membrane vesicles, referred to as "Salmonella"-induced filaments or SIF. SIF are highly dynamic in nature and extension, retraction, breaking and joining of membrane tubules were observed. The "Salmonella" pathogenicity island 2-encoded type III secretion system (SPI2-T3SS) is the main virulence factor for these phenotypes. A large number of effector proteins are translocated by the SPI2-T3SS. Live cell imaging and electron microscopy were applied to the analyses of the role of individual effectors. Here we report the role of various effector proteins of the SPI2-T3SS in the SIF dynamics and their phenotypic appearance. In contrast to analyses in fixed cells, the SIF induced by "sseF"- or "sseG"-deficient strains were not discontinuous, but rather continuous and thinner in diameter if analyzed in living host cells. A very dramatic difference was observed for a "pipB2"-deficient strain that induced very bulky, non-dynamic aggregations of membrane vesicles. Ultra-structural analyses also revealed a surprising complex nature of SIF. These membrane compartments, in part, entrapped cytoskeletal elements and were characterized by multiple membranes. Two types of SIF with lysosomal and non-lysosomal origin could be distinguished. The data of our analyses will lead to a revised view of the intracellular habitat of Salmonella and the molecular mechanisms of modification of host cells.