Evidence map›Paper›PMID 34460873›Full record

ArticlePLoS pathogens2021

Intracellular niche-specific profiling reveals transcriptional adaptations required for the cytosolic lifestyle of Salmonella enterica.

TuShun R Powers, Amanda L Haeberle, Alexander V Predeus, Disa L Hammarlöf, Jennifer A Cundiff, Zeus Saldaña-Ahuactzi, Karsten Hokamp, Jay C D Hinton, Leigh A Knodler

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 58 citations in OpenAlex.

  1. The Manipulation of Host Cells byInternational journal of molecular sciences · 2026
    Review
  2. Microbiology spectrum · 2026
    Article
  3. Review
  4. SLC11A2 withholds divalent metals fromProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. SLC11A2 affects nutritional immunity in the gut epithelium.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. TheVirulence · 2024
    Article
  17. Inflammasomes primarily restrict cytosolicbioRxiv : the preprint server for biology · 2024
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

TuShun R PowersPaul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.ORCID 0000-0003-0762-6316
Amanda L HaeberlePaul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
Alexander V PredeusInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-2750-1599
Disa L HammarlöfInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-8077-7615
Jennifer A CundiffPaul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.ORCID 0000-0002-3955-8226
Zeus Saldaña-AhuactziPaul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
Karsten HokampSmurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0001-7464-2370
Jay C D HintonInstitute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0003-2671-6026
Leigh A KnodlerPaul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.ORCID 0000-0002-3028-2198
Washington State University · USUniversity of Liverpool · GBTrinity College Dublin · IE

Funding

Infectious Diseases and Microbial Immunology Training ProgramT32AI007025 · NIAID · WASHINGTON STATE UNIVERSITY · PI Thomas H KAWULA, M KARIUKI NJENGA · 1985 to 2026
$7.4M
NIAID NIH HHS T32 AI007025
6 · The paper itself

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.

Indexed as

Adaptation, PhysiologicalGene Expression Regulation, BacterialVirulenceBacterial ProteinsCytosolGenomic IslandsHeLa CellsHumansRNA-SeqSalmonella entericaSalmonella InfectionsBacterial Proteins

Identifiers

PMID34460873
PMCPMC8432900
OpenAlexW3197348337

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.