Evidence map›Paper›PMID 41611701›Full record

ArticleNature communications2026

ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.

Isabel K Barter, Max J Bedding, Julia Leodolter, Joshua W C Maxwell, Paige M E Hawkins, Maxwell T Stevens, Matthew B McNeil, William J Jowsey, Trixie Wang, Diana Quan and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

18 authors.

Isabel K BarterSchool of Chemistry, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0009-0002-2284-9163
Max J BeddingSchool of Chemistry, The University of Sydney, Sydney, NSW, Australia.
Julia LeodolterResearch Institute of Molecular Pathology (IMP), Vienna, Austria.ORCID http://orcid.org/0000-0003-3632-056X
Joshua W C MaxwellSchool of Chemistry, The University of Sydney, Sydney, NSW, Australia.
Paige M E HawkinsSchool of Chemistry, The University of Sydney, Sydney, NSW, Australia.
Maxwell T StevensTuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-9876-003X
Matthew B McNeilDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0001-7747-7745
William J JowseyDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Trixie WangTuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia.
Diana QuanTuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia.
Sabryna JunkerResearch Institute of Molecular Pathology (IMP), Vienna, Austria.ORCID http://orcid.org/0000-0001-9846-4505
Manuela FlóridoCentenary Institute and Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Daniel HesselsonCentenary Institute and Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Gregory M CookDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0001-8349-1500
Tim ClausenResearch Institute of Molecular Pathology (IMP), Vienna, Austria.ORCID http://orcid.org/0000-0003-1582-6924
Warwick J BrittonTuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia. warwick.britton@sydney.edu.au.ORCID http://orcid.org/0000-0001-6721-9646
Mark LaranceCharles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. mark.larance@sydney.edu.au.ORCID http://orcid.org/0000-0002-8579-2267
Richard J PayneSchool of Chemistry, The University of Sydney, Sydney, NSW, Australia. richard.payne@sydney.edu.au.ORCID http://orcid.org/0000-0002-3618-9226

Funding

Department of Education and Training | Australian Research Council (ARC) CE200100012Department of Health | National Health and Medical Research Council (NHMRC) 1153493Department of Health | National Health and Medical Research Council (NHMRC) 1174941Department of Health | National Health and Medical Research Council (NHMRC) 2011467
6 · The paper itself

Abstract

Targeting the protein quality control system in Mycobacterium tuberculosis represents a promising and underexplored opportunity for antibiotic development. The ClpC1:ClpP1P2 protease is an essential component of the system that mediates both regulatory and stress-related protein degradation. Several non-ribosomal peptide natural products, including ecumicin, ilamycins (rufomycins) and cyclomarins, have been discovered that bind to the ClpC1 chaperone of the complex and exhibit potent antimycobacterial activity, leading to significant interest in the ClpC1:ClpP1P2 system as a bona fide target for the new tuberculosis drugs. In this study, we combine quantitative proteomics, bioinformatics, transcriptomics, CRISPRi knockdown, and targeted biochemical and biophysical assays to dissect the mechanisms of ecumicin, ilamycin and cyclomarin in clinically relevant Mycobacterium tuberculosis. Strikingly, despite exhibiting similar binding modes to ClpC1, each compound induces distinct effects on protein degradation. Notably, ilamycin and ecumicin do not trigger the ClpC2 rescue mechanism that mitigates cyclomarin-induced mycobacterial toxicity. In addition, we identify a novel interaction between ecumicin and stress-response chaperone Hsp20. The differential disruption of ClpC1 substrates, stress-response chaperones, and distinct reshaping of the Mycobacterium tuberculosis proteome by the three natural products, unveils new opportunities for the development of protein quality control-targeted antimycobacterials.

Indexed as

Bacterial ProteinsBiological ProductsHeat-Shock ProteinsMycobacterium tuberculosisPeptidesProteomeAntitubercular AgentsOligopeptidesProteolysisProteomicsAntitubercular AgentsBacterial ProteinsBiological ProductsClpC1 protein, Mycobacterium tuberculosisHeat-Shock ProteinsOligopeptidesPeptidesProteomerufomycin

Identifiers

PMID41611701
PMCPMC12913811

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.