In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2021-8-30), p. e1009280-
Abstract:
Salmonella enterica serovar Typhimurium ( S . Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, S . Typhimurium colonizes epithelial cells lining the gastrointestinal tract. S . Typhimurium has an unusual lifestyle in epithelial cells that begins within an endocytic-derived Salmonella -containing vacuole (SCV), followed by escape into the cytosol, epithelial cell lysis and bacterial release. The cytosol is a more permissive environment than the SCV and supports rapid bacterial growth. The physicochemical conditions encountered by S . Typhimurium within the epithelial cytosol, and the bacterial genes required for cytosolic colonization, remain largely unknown. Here we have exploited the parallel colonization strategies of S . Typhimurium in epithelial cells to decipher the two niche-specific bacterial virulence programs. By combining a population-based RNA-seq approach with single-cell microscopic analysis, we identified bacterial genes with cytosol-induced or vacuole-induced expression signatures. Using these genes as environmental biosensors, we defined that Salmonella is exposed to oxidative stress and iron and manganese deprivation in the cytosol and zinc and magnesium deprivation in the SCV. Furthermore, iron availability was critical for optimal S . Typhimurium replication in the cytosol, as well as entC , fepB , soxS , mntH and sitA . Virulence genes that are typically associated with extracellular bacteria, namely Salmonella pathogenicity island 1 (SPI1) and SPI4, showed increased expression in the cytosol compared to vacuole. Our study reveals that the cytosolic and vacuolar S . Typhimurium virulence gene programs are unique to, and tailored for, residence within distinct intracellular compartments. This archetypical vacuole-adapted pathogen therefore requires extensive transcriptional reprogramming to successfully colonize the mammalian cytosol.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009280
DOI:
10.1371/journal.ppat.1009280.g001
DOI:
10.1371/journal.ppat.1009280.g002
DOI:
10.1371/journal.ppat.1009280.g003
DOI:
10.1371/journal.ppat.1009280.g004
DOI:
10.1371/journal.ppat.1009280.g005
DOI:
10.1371/journal.ppat.1009280.g006
DOI:
10.1371/journal.ppat.1009280.g007
DOI:
10.1371/journal.ppat.1009280.g008
DOI:
10.1371/journal.ppat.1009280.t001
DOI:
10.1371/journal.ppat.1009280.s001
DOI:
10.1371/journal.ppat.1009280.s002
DOI:
10.1371/journal.ppat.1009280.s003
DOI:
10.1371/journal.ppat.1009280.s004
DOI:
10.1371/journal.ppat.1009280.s005
DOI:
10.1371/journal.ppat.1009280.s006
DOI:
10.1371/journal.ppat.1009280.s007
DOI:
10.1371/journal.ppat.1009280.s008
DOI:
10.1371/journal.ppat.1009280.s009
DOI:
10.1371/journal.ppat.1009280.s010
DOI:
10.1371/journal.ppat.1009280.s011
DOI:
10.1371/journal.ppat.1009280.s012
DOI:
10.1371/journal.ppat.1009280.s013
DOI:
10.1371/journal.ppat.1009280.s014
DOI:
10.1371/journal.ppat.1009280.r001
DOI:
10.1371/journal.ppat.1009280.r002
DOI:
10.1371/journal.ppat.1009280.r003
DOI:
10.1371/journal.ppat.1009280.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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