![]() ![]() After invasion or phagocytic uptake, STM initiates a complex intracellular lifestyle enabling survival and proliferation within host cells. enterica serovar Typhimurium (STM) is commonly used to investigate the intracellular lifestyle of Salmonella. Salmonella enterica is a Gram-negative, foodborne bacterial pathogen, causing diseases ranging from severe typhoid fever to self-limiting gastrointestinal infections in various hosts. For this purpose, pathogens translocate, by different secretion systems, specific effector proteins that manipulate the host cell endosomal system 1. Biogenesis of specialized pathogen-containing vacuoles depends on recruitment of subsets of host cell endosomes in order to establish nutritional supply, and to evade the host immune defense. Within these organelles, pathogens are able to adopt specific intracellular lifestyles. Various intracellular pathogens are confined to membrane-bound compartments. This mechanism controls membrane deformation and vesicular fusion to generate the specific intracellular niche for bacterial survival and proliferation. ![]() Effector-positive vesicles continuously fuse with SCV and SIF membranes, providing a route of effector delivery by translocation, interaction with endosomal vesicles, and ultimately fusion with the continuum of SCV/SIF membranes. In the early infection, host endosomal vesicles are associated with Salmonella effectors. Dynamics differ between various effectors investigated and is dependent on membrane architecture of SIF. Translocated effectors diffuse in membranes of SIF with mobility comparable to membrane-integral host proteins in endomembranes. We deployed self-labeling enzyme tags to label translocated effectors in living host cells, and analyzed their single molecule dynamics. ![]() How effectors reach their subcellular destination, and how they interact with endomembranes remodeled by Salmonella remains to be determined. A subset of effectors is associated with, or integral in SCV and SIF membranes. The intracellular lifestyle of Salmonella critically depends on effector proteins translocated into host cells. Salmonella resides within the Salmonella-containing vacuole (SCV) and by Salmonella-induced fusions of host endomembranes, the SCV is connected with extensive tubular structures termed Salmonella-induced filaments (SIF).
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