Evidence map›Paper›PMID 39532967›Full record

ArticleScientific reports2024

Assessing the propensity of TB clinical isolates to form viable but non-replicating subpopulations.

Julian L Coetzee, Nastassja L Kriel, Johannes Loubser, Anzaan Dippenaar, Samantha L Sampson, Stephanus T Malherbe, Jacoba M Mouton

Erratum issuedAbstract read
In one paragraph

Article in Scientific reports, 2024. 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 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. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Julian L CoetzeeDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
Nastassja L KrielDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa. nastassja@sun.ac.za.
Johannes LoubserDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
Anzaan DippenaarDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
Samantha L SampsonDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
Stephanus T MalherbeDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
Jacoba M MoutonDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.

Funding

Fonds Wetenschappelijk Onderzoek G0F8316NNational Research Foundation 86539
6 · The paper itself

Abstract

Current tuberculosis (TB) treatment is typically effective against drug-susceptible Mycobacterium tuberculosis, but can fail due to acquired drug resistance or phenotypic resistance. M. tuberculosis persisters, a subpopulation of viable but non-replicating (VBNR) antibiotic-tolerant bacteria, are thought to contribute to poor TB treatment outcomes. In this exploratory study, we investigated treatment-naïve drug-susceptible clinical isolates collected from people with TB, who subsequently had unsuccessful treatment outcomes. These were compared to isolates from cured individuals in terms of their ability to form VBNR subpopulations. Clinical isolates from individuals with unfavorable treatment outcomes form larger subpopulations of VBNR M. tuberculosis (2.67-13.71%) than clinical isolates from cured cases (0- 1.63%) following infection of THP-1 macrophages. All isolates were drug susceptible based on phenotypic and genotypic analysis. Whole genome sequencing identified 23 non-synonymous genomic variants shared by treatment failure clinical isolates, that were not present in isolates from cured cases. This exploratory study highlights the ability of treatment-naïve clinical isolates to form heterogeneous populations containing VBNR M. tuberculosis. We also demonstrate that clinical isolates from individuals with unsuccessful treatment outcomes form higher percentages of VBNR M. tuberculosis. The findings of this exploratory study suggest that an increased propensity to form VBNR subpopulations may impact TB treatment outcome.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisTuberculosisDrug Resistance, BacterialGenotypeHumansMicrobial Sensitivity TestsTHP-1 CellsWhole Genome SequencingAntitubercular AgentsHeterogenousPersistencePersisterTBTreatment failureTuberculosisVBNR

Identifiers

PMID39532967
PMCPMC11557868

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LicenceCC BY-NC-ND
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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.