Evidence map›Paper›PMID 41974676›Full record

ArticleNature communications2026

Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis.

Matthew Silcocks, James P Lingford, Chen-Yi Cheung, William J Jowsey, Rita M McCall, Christopher D Rae, Liam K Harold, David Edwards, Evan Pepper-Tunick, Stephanie L Neville and 15 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Frontiers in cellular and infection microbiology · 2026
    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

25 authors.

Matthew SilcocksDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia. m.silcocks@unimelb.edu.au.ORCID http://orcid.org/0000-0002-1527-5168
James P LingfordDepartment of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Chen-Yi CheungDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
William J JowseyDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Rita M McCallDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-5076-2909
Christopher D RaeDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.
Liam K HaroldDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0002-7570-7348
David EdwardsDepartment of Infectious Diseases, School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Evan Pepper-TunickInstitute for Systems Biology, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3841-9099
Stephanie L NevilleDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Megan J MaherSchool of Chemistry, Department of Biochemistry and Pharmacology and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-0848-9640
Aleix Canalda-BaltronsDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-8366-7377
Xuling ChangDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-7471-4768
Phan Vuong Khac ThaiTam Tri Sai Gon Hospital, District 12, Ho Chi Minh City, Vietnam.
Kathryn E HoltDepartment of Infectious Diseases, School of Translational Medicine, Monash University, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-3949-2471
Nitin S BaligaInstitute for Systems Biology, Seattle, WA, USA.
Gregory M CookDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Thomas R HawnDepartment of Medicine, University of Washington, Seattle, WA, USA.
Nguyen Thuy Thuong ThuongOxford University Clinical Research Unit, Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam.ORCID http://orcid.org/0000-0001-8733-692X
Maxine CawsLiverpool School of Tropical Medicine, Liverpool, UK.
Chris GreeningDepartment of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0001-7616-0594
Christopher A McDevittDepartment of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-1596-4841
Jeffery S CoxDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-5061-6618
Matthew B McNeilDepartment of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0001-7747-7745
Sarah J DunstanDepartment of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia. sarah.dunstan@unimelb.edu.au.ORCID http://orcid.org/0000-0001-7873-933X

Funding

Department of Health | National Health and Medical Research Council (NHMRC) APP1172853
6 · The paper itself

Abstract

Phenotypically agnostic screens for positive selection in pathogen populations provide a means of pinpointing genes and regulatory regions involved in adaptation to the local environment or host population. We screened a large (n = 2506) collection of Vietnamese Mycobacterium tuberculosis (Mtb) isolates, finding targets of selection to be lineage-specific, and encompass diverse functions, including dormancy (Rv0080), zinc homeostasis (zur), and virulence (ESX-1 structure). Extending our screen to the wider Mtb complex (MTBC) phylogeny demonstrated Rv0080 to display an extraordinarily dynamic evolutionary history, acquiring premature stop codons or putative functional mutations on branches upstream of 8 of the 10 human-adapted lineages, and undergoing positive selection in the remaining 2. Lineage 1, which is one of two such lineages retaining the ancestral Rv0080 sequence, displays a rate of selection for this gene (dN/dS=9.37) exceeding any other in the Mtb genome, save a transcription factor linked to its expression (Rv0042c; dN/dS=11.02). Deletion of Rv0080's M. smegmatis orthologue confers a survival advantage in hypoxic conditions, as does the evolution of nonsense or missense mutations on an ancestral Rv0080 background. We show the dormancy survival regulon experienced recurrent episodes of reductive evolution across the MTBC phylogeny, illuminating a novel mechanism via which it adapted to human populations.

Indexed as

Bacterial ProteinsEvolution, MolecularMycobacterium tuberculosisRegulonGene Expression Regulation, BacterialHumansPhylogenyBacterial Proteins

Identifiers

PMID41974676
PMCPMC13284343

What OpenQuestion holds

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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.