A SUMOylation dependent switch of Rab7 governs intracellular life and pathogenesis of Salmonella Typhimurium.

Salmonella Typhimurium (ST) is an intracellular pathogen that causes gastroenteritis in humans. Aided by a battery of effector proteins, ST resides intracellularly in a specialized vesicle, called Salmonella -containing vacuole (SCV) that utilizes the host endocytic vesicular-transport pathway (VTP). Here we probed the possible role of SUMOylation, a post-translation modification pathway, in SCV biology. Proteome analysis by complex mass-spectrometry (MS/MS) revealed a dramatically altered SUMO-proteome (SUMOylome) in ST infected cells. Rab7, a component of VTP, was key among several crucial proteins identified in our study. Detailed MS/MS along with in vitro SUMOylation assays and structural docking analysis revealed SUMOylation of Rab7 specifically at Lysine-175. A SUMOylation deficient Rab7 mutant (Rab7K175R ) displayed longer half-life, was beneficial to SCV dynamics and functionally blemished. Collectively the data revealed that Rab7 SUMOylation blockade by ST ensures availability of long-lived but functionally compromised Rab7 which was beneficial to the pathogen. Overall this SUMOylation dependent switch of Rab7 controlled by ST is an unexpected mode of VTP pathway regulation, and unveils mechanism of broad interest well beyond Salmonella -host crosstalk.