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- W4387165037 endingPage "e1011686" @default.
- W4387165037 startingPage "e1011686" @default.
- W4387165037 abstract "One of the mechanisms shaping the pathophysiology during the infection of enteric pathogen Salmonella Typhimurium is host PTM machinery utilization by the pathogen encoded effectors. Salmonella Typhimurium ( S . Tm) during infection in host cells thrives in a vacuolated compartment, Salmonella containing vacuole (SCV), which sequentially acquires host endosomal and lysosomal markers. Long tubular structures, called as Salmonella induced filaments (SIFs), are further generated by S . Tm, which are known to be required for SCV’s nutrient acquisition, membrane maintenance and stability. A tightly coordinated interaction involving prominent effector SifA and various host adapters PLEKHM1, PLEKHM2 and Rab GTPases govern SCV integrity and SIF formation. Here, we report for the first time that the functional regulation of SifA is modulated by PTM SUMOylation at its 11 th lysine. S . Tm expressing SUMOylation deficient lysine 11 mutants of SifA (SifA K11R ) is defective in intracellular proliferation due to compromised SIF formation and enhanced lysosomal acidification. Furthermore, murine competitive index experiments reveal defective in vivo proliferation and weakened virulence of SifA K11R mutant. Concisely, our data reveal that SifA K11R mutant nearly behaves like a SifA knockout strain which impacts Rab9-MPR mediated lysosomal acidification pathway, the outcome of which culminates in reduced bacterial load in in vitro and in vivo infection model systems. Our results bring forth a novel pathogen-host crosstalk mechanism where the SUMOylation of effector SifA regulated S . Tm intracellular survival." @default.
- W4387165037 created "2023-09-30" @default.
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- W4387165037 date "2023-09-29" @default.
- W4387165037 modified "2023-10-14" @default.
- W4387165037 title "SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function" @default.
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- W4387165037 doi "https://doi.org/10.1371/journal.ppat.1011686" @default.
- W4387165037 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37773952" @default.
- W4387165037 hasPublicationYear "2023" @default.
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