ArticleGenome biology2017
The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.
Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Quantifying within-household tuberculosis transmission: a systematic review and prospective cohort study.International journal of epidemiology · 2026Pooled it
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- Polyketide synthase 12 is anbioRxiv : the preprint server for biology · 2026Article
- Population-level genome sequencing reveals distinctmSystems · 2026Article
- Rapid detection of treatment-emergent resistance to bedaquiline and pretomanid inMicrobiology spectrum · 2026Article
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Within-host pathogen population diversity predicts treatment response in Tuberculosis.medRxiv : the preprint server for health sciences · 2026Article
- Long-term spatiotemporal evolution of drug-resistant Mycobacterium tuberculosis in China.Nature communications · 2026Article
- Population-level genome sequencing reveals distinct Mycobacterium tuberculosis intrahost mutational trajectories in simian immunodeficiency virus co-infected and antiretroviral treated non-human primates.bioRxiv : the preprint server for biology · 2026Article
- Benchmarking within-sample minority variant detection with short-read sequencing inbioRxiv : the preprint server for biology · 2026Article
- Genomic characterization of drug-resistantFrontiers in tuberculosis · 2026Article
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.Tuberculosis (Edinburgh, Scotland) · 2025Article
- Cross-continental transmission and host adaptation ofiMetaOmics · 2025Article
- Article
- Ongoing evolution of PE/PPE genes inmSystems · 2025Article
- Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex.Nature reviews. Microbiology · 2025Review
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection inbioRxiv : the preprint server for biology · 2025Article
- Loss of theScience advances · 2025Article
- Genomic Analysis of Global Mycobacterium abscessus Isolates Reveals Ongoing Evolution of Drug Resistance-Associated Genes.The Journal of infectious diseases · 2025Article
- Advantages of updated WHO mutation catalog combined with existing whole-genome sequencing-based approaches for Mycobacterium tuberculosis resistance prediction.Genome medicine · 2025Article
26 more citing papers are in PubMed but not listed here.
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20 authors.
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Abstract
backgroundCombination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics.
resultsBy combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance.
conclusionsOur findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.
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