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SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function
 
Creator Chandrsekhar, Hridya
Mohapatra, Gayatree
Kajal, Kirti
Singh, Mukesh
Walia, Kshitiz
Rana, Sarika
Kaur, Navneet
Sharma, Sheetal
Tuli, Amit
Das, Prasenjit
Srikanth, Chittur V
 
Subject QR Microbiology
 
Description 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 11th lysine. S. Tm expressing SUMOylation deficient lysine 11 mutants of 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 data reveal that SifAK11R 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.
 
Publisher Public Library of Science (PLoS)
 
Date 2023-09-29
 
Type Article
PeerReviewed
 
Relation https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011686
http://crdd.osdd.net/open/3168/
 
Identifier Chandrsekhar, Hridya and Mohapatra, Gayatree and Kajal, Kirti and Singh, Mukesh and Walia, Kshitiz and Rana, Sarika and Kaur, Navneet and Sharma, Sheetal and Tuli, Amit and Das, Prasenjit and Srikanth, Chittur V (2023) SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function. PLoS Pathogens, 19 (9). ISSN 1553-7374