Evidence map›Paper›PMID 28119503›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions.

William H Conrad, Morwan M Osman, Jonathan K Shanahan, Frances Chu, Kevin K Takaki, James Cameron, Digby Hopkinson-Woolley, Roland Brosch, Lalita Ramakrishnan

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed
18.0field-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

154 citing papers in PubMed, 256 citations in OpenAlex.

  1. Article
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  6. HowVaccines · 2026
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  14. Journal of bacteriology · 2025
    Review
  15. Article
  16. Article
  17. Single-cell analysis revealsScience advances · 2025
    Article
  18. The N-terminal domain ofFrontiers in immunology · 2025
    Article
  19. Review
  20. WhiB-like proteins: Diversity of structure, function and mechanism.Biochimica et biophysica acta. Molecular cell research · 2024
    Review

94 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

9 authors at 4 institutions in 3 countries.

William H ConradDepartment of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
Morwan M OsmanDepartment of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
Jonathan K ShanahanDepartment of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
Frances ChuDepartment of Microbiology, University of Washington, Seattle, WA 98105.
Kevin K TakakiDepartment of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom.
James CameronDepartment of Microbiology, University of Washington, Seattle, WA 98105.
Digby Hopkinson-WoolleyDepartment of Biology, Eton College, Windsor SL4 6DW, United Kingdom.
Roland BroschUnit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, 75015 Paris, France.ORCID 0000-0003-2587-3863
Lalita RamakrishnanDepartment of Medicine, University of Cambridge, Cambridge CB2 0QH, United Kingdom; lr404@cam.ac.uk.
University of Washington · USUniversity of Cambridge · GBEton College · GBInstitut Pasteur · FR

Funding

Host-Responses to Mycobacterium Infection in ZebrafishR37AI054503 · NIAID · UNIVERSITY OF WASHINGTON · PI RAMAKRISHNAN, LALITA · 2012 to 2021
$3.1M
INTERDISCIPLINARY PROGRAM IN BACTERIAL PATHOGENESIST32AI055396 · NIAID · UNIVERSITY OF WASHINGTON · PI FANG, FERRIC C · 2003 to 2019
$2.8M
NIAID NIH HHS R37 AI054503NIAID NIH HHS T32 AI055396Wellcome Trust
6 · The paper itself

Abstract

Mycobacterium tuberculosis and Mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. The type VII secretion system ESX-1 [6-kDa early secretory antigenic target (ESAT-6) secretion system 1] is required for both virulence and host cell membrane lysis. Both activities are attributed to the pore-forming activity of the ESX-1-secreted substrate ESAT-6 because multiple studies have reported that recombinant ESAT-6 lyses eukaryotic membranes. We too find ESX-1 of M. tuberculosis and M. marinum lyses host cell membranes. However, we find that recombinant ESAT-6 does not lyse cell membranes. The lytic activity previously attributed to ESAT-6 is due to residual detergent in the preparations. We report here that ESX-1-dependent cell membrane lysis is contact dependent and accompanied by gross membrane disruptions rather than discrete pores. ESX-1-mediated lysis is also morphologically distinct from the contact-dependent lysis of other bacterial secretion systems. Our findings suggest redirection of research to understand the mechanism of ESX-1-mediated lysis.

Indexed as

HemolysisAnimalsAntigens, BacterialBacterial AdhesionBacterial ProteinsBacterial Secretion SystemsCell LineCell Line, TumorErythrocyte MembraneErythrocytesHost-Pathogen InteractionsHumansLarvaMacrophagesMiceMycobacterium marinumAntigens, BacterialBacterial ProteinsBacterial Secretion SystemsESAT-6 protein, Mycobacterium tuberculosiscell membrane lysisESAT-6ESX-1 secretion systemMycobacterium marinumMycobacterium tuberculosis

Identifiers

PMID28119503
PMCPMC5307465
OpenAlexW2581461126

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.