Evidence map›Paper›PMID 27078095›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

The type III secretion system apparatus determines the intracellular niche of bacterial pathogens.

Juan Du, Analise Z Reeves, Jessica A Klein, Donna J Twedt, Leigh A Knodler, Cammie F Lesser

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

62 citing papers in PubMed, 126 citations in OpenAlex.

  1. Profiling Selectivity for theBiochemistry · 2026
    Article
  2. Article
  3. Article
  4. IntracellularProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. TheVirulence · 2024
    Article
  11. Article
  12. Review
  13. Article
  14. Evidence for intracellularJournal of bacteriology · 2024
    Review
  15. Regulation of virulence inFrontiers in microbiology · 2024
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article

2 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Juan DuDepartment of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA 02139; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
Analise Z ReevesDepartment of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA 02139; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
Jessica A KleinPaul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
Donna J TwedtPaul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
Leigh A KnodlerPaul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164 CLESSER@mgh.harvard.edu lknodler@vetmed.wsu.edu.
Cammie F LesserDepartment of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA 02139; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; CLESSER@mgh.harvard.edu lknodler@vetmed.wsu.edu.
Massachusetts General Hospital · USWashington State University · US

Funding

Modeling mechanisms of Shigella pathogenesis in yeastR01AI064285 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LESSER, CAMMIE · 2006 to 2017
$4.0M
Shigella suppression of epithelial cell deathR56AI064285 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LESSER, CAMMIE · 2012 to 2022
$948k
Anti-inflammatory promoting commensal E. coliR21AI103882 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LESSER, CAMMIE · 2013 to 2014
$477k
NIAID NIH HHS R01 AI064285NIAID NIH HHS R21 AI103882NIAID NIH HHS R56 AI064285
6 · The paper itself

Abstract

Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functional Shigella type III secretion system, but none of its effectors, into a laboratory strain of Escherichia coli is sufficient to promote the efficient vacuole lysis and escape of the modified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for the Shigella type III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain of Yersinia remains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA of Shigella, Salmonella, and Chromobacterium, we demonstrate that a single protein component of the T3SA translocon-Shigella IpaC, Salmonella SipC, or Chromobacterium CipC-determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established.

Indexed as

Gram-Negative BacteriaHeLa CellsHost-Pathogen InteractionsHumansPhagosomesType III Secretion SystemsType III Secretion Systemsphagosomal escapeSalmonellaShigellatype III secretion systemvacuole lysis

Identifiers

PMID27078095
PMCPMC4855615
OpenAlexW2340892849

What OpenQuestion holds

Textmetadata
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.