Contribution of bacterial effectors and host proteins to the composition and function of Salmonella-induced tubules.

Cells infected with Salmonella are characterised by the appearance of membrane tubular structures that stretch from the bacterial vacuole. The formation of these tubules requires the translocation of Salmonella effector proteins within the infected cell. Different types of Salmonella-induced tubules with varying host protein compositions have been identified. This variability probably reflects the ability of these tubules to interact with different host compartments. Membrane tubules decorated with effector proteins but essentially devoid of host proteins and named LAMP1-negative (LNT) were observed. LNTs wrap around LAMP1-positive vesicles and may promote recruitment of lysosomal glycoproteins to bacterial vacuole and the formation of a replication niche. We conducted a biochemical and functional characterisation of LNTs. We show that the effector proteins SseF and SseG are necessary for their formation. The absence of these tubules is associated with decreased recruitment of LAMP1 to SCVs, decreased intracellular replication of Salmonella, and decreased virulence in mice. We found that the process leading to the recruitment of lysosomal glycoproteins to tubules involves the C-terminal domain of the effector protein SifA and the GTPase Arl8b. Overall, these data suggest that Salmonella-induced tubules promote the establishment of the replication niche by promoting recruitment of host proteins to the bacterial vacuole.

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