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

SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function
type: AcademicArticle
type: Article
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 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.
date: 2023-09-29
volume: 19
issue: 9
is part of: PLoS Pathogens
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Public Library of Science (PLoS)
type: Organization

PLoS Pathogens
type: Collection
issn: 15537374

Prasenjit Das
type: Person
given name: Prasenjit
family name: Das

Kshitiz Walia
type: Person
given name: Kshitiz
family name: Walia

Mukesh Singh
type: Person
given name: Mukesh
family name: Singh

Sheetal Sharma
type: Person
given name: Sheetal
family name: Sharma

Amit Tuli
type: Person
given name: Amit
family name: Tuli

Navneet Kaur
type: Person
given name: Navneet
family name: Kaur

Kirti Kajal
type: Person
given name: Kirti
family name: Kajal

Hridya Chandrsekhar
type: Person
given name: Hridya
family name: Chandrsekhar

Sarika Rana
type: Person
given name: Sarika
family name: Rana

Chittur V Srikanth
type: Person
given name: Chittur V
family name: Srikanth

Gayatree Mohapatra
type: Person
given name: Gayatree
family name: Mohapatra

HTML Summary of #3168 SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function
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primary topic: SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function

QR Microbiology
type: Concept