Evidence map›Paper›PMID 25938982›Full record

ArticlePLoS genetics2015

Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria.

Louis S Ates, Roy Ummels, Susanna Commandeur, Robert van de Weerd, Robert van der Weerd, Marion Sparrius, Eveline Weerdenburg, Marina Alber, Rainer Kalscheuer, Sander R Piersma and 7 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 122 papers.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed
11.3field-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

122 citing papers in PubMed, 188 citations in OpenAlex.

  1. The mycomembrane proteins PorH and ProtX are inserted at polar growth zones and linked to the cell wall.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Tyloxapol inhibits ESX-1 secretion inJournal of bacteriology · 2026
    Article
  5. Article
  6. Article
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  8. Article
  9. ThemBio · 2026
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Control of antigen presentation on MHC-I by a bacterial secretion system.bioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
  18. A widespread family of molecular chaperones promotes the intracellular stability of type VIIb secretion system-exported toxins.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Loss of the ESX-5 secretion locus inProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Journal of bacteriology · 2025
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 3 countries.

Louis S AtesDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Roy UmmelsDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Susanna CommandeurDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Robert van de Weerd
Robert van der WeerdDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Marion SparriusDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Eveline WeerdenburgDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands.
Marina AlberInstitute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Rainer KalscheuerInstitute for Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Sander R PiersmaDepartment of Medical Oncology, OncoProteomics Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
Abdallah M AbdallahBiological and Environmental Sciences and Engineering (BESE) division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Moataz Abd El GhanyBiological and Environmental Sciences and Engineering (BESE) division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Alyaa M Abdel-HaleemBiological and Environmental Sciences and Engineering (BESE) division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Arnab PainBiological and Environmental Sciences and Engineering (BESE) division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Connie R JiménezDepartment of Medical Oncology, OncoProteomics Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
Wilbert BitterDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, the Netherlands; Section Molecular Microbiology, Amsterdam Institute of Molecules, Medicine & Systems, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Edith N G HoubenSection Molecular Microbiology, Amsterdam Institute of Molecules, Medicine & Systems, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Amsterdam UMC Location VUmc · NLKing Abdullah University of Science and Technology · SAHeinrich Heine University Düsseldorf · DEVrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of MspA-like porins in slow-growing mycobacteria.

Indexed as

Gene Expression Regulation, BacterialAmpicillinBacterial ProteinsCell Membrane PermeabilityChromatography, LiquidDNA, BacterialDNA Transposable ElementsDrug Resistance, BacterialMutationMycobacterium bovisMycobacterium marinumMycobacterium tuberculosisSequence Analysis, DNATandem Mass SpectrometryType VII Secretion SystemsAmpicillinBacterial ProteinsDNA, BacterialDNA Transposable ElementsType VII Secretion Systems

Identifiers

PMID25938982
PMCPMC4418733
OpenAlexW1508212288

What OpenQuestion holds

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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.