ArticleGenome biology2014
Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- ClinicalFrontiers in microbiology · 2025Pooled it
- Mathematical models of drug-resistant tuberculosis lack bacterial heterogeneity: A systematic review.PLoS pathogens · 2024Pooled it
- Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review.BMC medicine · 2016Pooled it
- Benchmarking within-sample minority variant detection with short-read sequencing inbioRxiv : the preprint server for biology · 2026Article
- Tuberculosis: An Ongoing Global Threat.Advances in experimental medicine and biology · 2026Review
- Experimental evolution in an era of molecular manipulation.Nature reviews. Genetics · 2026Review
- Recurrent gene conversions and subcluster-specific variants are associated withFrontiers in microbiology · 2026Article
- Genomic characterization of XDR Mycobacterium tuberculosis isolates in Argentina (2006-2015).BMC infectious diseases · 2025Article
- Genomic characterisation of recurrent Mycobacterium avium isolates from chronically infected patients reveals patterns of within-host evolution.Genome medicine · 2025Article
- South Asian origin and global transmission history ofmSystems · 2025Article
- Bayesian phylodynamic inference of population dynamics with dormancy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Bayesian phylodynamic inference of population dynamics with dormancy.bioRxiv : the preprint server for biology · 2025Article
- Molecular typing of Mycobacterium tuberculosis: a review of current methods, databases, softwares, and analytical tools.FEMS microbiology reviews · 2025Review
- Within-host population dynamics of extensively drug-resistantEvolution, medicine, and public health · 2025Article
- Drug selection based on pan-genomics genetic features ofFrontiers in microbiology · 2025Article
- From Petri Dishes to Patients to Populations: Scales and Evolutionary Mechanisms Driving Antibiotic Resistance.Annual review of microbiology · 2024Review
- Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.Nature reviews. Microbiology · 2024Review
- A study on factors influencing delayed sputum conversion in newly diagnosed pulmonary tuberculosis based on bacteriology and genomics.Scientific reports · 2024Article
- Genetic mechanisms of co-emergence of INH-resistantMicrobiology spectrum · 2024Article
- Genotype-Phenotype Characterization of Serial Mycobacterium tuberculosis Isolates in Bedaquiline-Resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMycobacterium tuberculosis is characterized by a low mutation rate and a lack of genetic recombination. Yet, the rise of extensively resistant strains paints a picture of a microbe with an impressive adaptive potential. Here we describe the first documented case of extensively drug-resistant tuberculosis evolved from a susceptible ancestor within a single patient.
resultsGenome sequences of nine serial M. tuberculosis isolates from the same patient uncovered a dramatic turnover of competing lineages driven by the emergence, and subsequent fixation or loss of single nucleotide polymorphisms. For most drugs, resistance arose through independent emergence of mutations in more than one clone, of which only one ultimately prevailed as the clone carrying it expanded, displacing the other clones in the process. The vast majority of mutations identified over 3.5 years were either involved in drug resistance or hitchhiking in the genetic background of these. Additionally, RNA-sequencing of isolates grown in the absence of drug challenge revealed that the efflux-associated iniBAC operon was up-regulated over time, whereas down-regulated genes include those involved in mycolic acid synthesis.
conclusionsWe observed both rapid acquisitions of resistance to antimicrobial compounds mediated by individual mutations as well as a gradual increase in fitness in the presence of antibiotics, likely driven by stable gene expression reprogramming. The rapid turnover of resistance mutations and hitchhiking neutral mutations has major implications for inferring tuberculosis transmission events in situations where drug resistance evolves within transmission chains.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.