SifA SUMOylation governs Salmonella intracellular survival via modulation of lysosomal function

Abstract

Gastroenteritis causing pathogen Salmonella Typhimurium (S. Tm) during its 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 known to be required for SCVs nutrient acquisition, membrane maintenance and stability. A tightly coordinated interactions 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, the functional regulation of SifA is modulated by its SUMOylation at lysine 11. S. Tm expressing lysine 11 mutant SifA (SifAK11R) 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 SifAK11R mutant. Concisely, our results demonstrate that SUMO deficient SifA mutant nearly behaves like a SifA knockout strain which impacts PLEKHM2-M6PR mediated lysosomal acidification pathway. Thus, our results bring forth a novel S. Tm-host crosstalk mechanism involving host mediated effector SUMOylation critical for pathogenicity.