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

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

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 t...

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Bibliographic Details
Published in:Scientific reports Vol. 14; no. 1; pp. 27686 - 12
Main Authors: Coetzee, Julian L., Kriel, Nastassja L., Loubser, Johannes, Dippenaar, Anzaan, Sampson, Samantha L., Malherbe, Stephanus T., Mouton, Jacoba M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12-11-2024
Nature Publishing Group
Nature Portfolio
Subjects:
631/326
631/326/41
631/326/421
692/699/255
Clinical isolates
Clinical outcomes
Drug resistance
Genomic analysis
Heterogenous
Humanities and Social Sciences
Macrophages
multidisciplinary
Persistence
Persister
Population studies
Science
Science (multidisciplinary)
Subpopulations
Tuberculosis
VBNR
Whole genome sequencing
Persistence
Tuberculosis
VBNR
Treatment failure
Persister
TB
Heterogenous
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-79389-w