ArticleAntimicrobial agents and chemotherapy2008
Convergent evolutionary analysis identifies significant mutations in drug resistance targets of Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2014Pooled it
- Polyketide synthases mutation in tuberculosis transmission revealed by whole genomic sequence, China, 2011-2019.Frontiers in genetics · 2023Article
- Article
- Mutations in dnaA and a cryptic interaction site increase drug resistance in Mycobacterium tuberculosis.PLoS pathogens · 2020Article
- Validation of Novel Mycobacterium tuberculosis Isoniazid Resistance Mutations Not Detectable by Common Molecular Tests.Antimicrobial agents and chemotherapy · 2018Article
- Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam.Nature genetics · 2018Article
- Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations.Scientific reports · 2018Article
- Clinical and bacteriological characteristics associated with clustering of multidrug-resistant tuberculosis.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2017Article
- Spatial and Temporal Control of Evolution through Replication-Transcription Conflicts.Trends in microbiology · 2017Article
- Evolution of drug resistance in tuberculosis: recent progress and implications for diagnosis and therapy.Drugs · 2014Review
- Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes.Nature genetics · 2011Article
- Simultaneous identification of mycobacterial isolates to the species level and determination of tuberculosis drug resistance by PCR followed by electrospray ionization mass spectrometry.Journal of clinical microbiology · 2011Article
- Mutations in extensively drug-resistant Mycobacterium tuberculosis that do not code for known drug-resistance mechanisms.The Journal of infectious diseases · 2010Article
- Selection of mutations to detect multidrug-resistant Mycobacterium tuberculosis strains in Shanghai, China.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis adapts to the environment by selecting for advantageous single-nucleotide polymorphisms (SNPs). We studied whether advantageous SNPs could be distinguished from neutral mutations within genes associated with drug resistance. A total of 1,003 clinical isolates of M. tuberculosis were related phylogenetically and tested for the distribution of SNPs in putative drug resistance genes. Drug resistance-associated versus non-drug-resistance-associated SNPs in putative drug resistance genes were compared for associations with single versus multiple-branch outcomes using the chi-square and Fisher exact tests. All 286 (100%) isolates containing isoniazid (INH) resistance-associated SNPs had multibranch distributions, suggestive of multiple ancestry and convergent evolution. In contrast, all 327 (100%) isolates containing non-drug-resistance-associated SNPs were monophyletic and thus showed no evidence of convergent evolution (P < 0.001). Convergence testing was then applied to SNPs at position 481 of the iniA (Rv0342) gene and position 306 of the embB gene, both potential drug resistance targets for INH and/or ethambutol. Mutant embB306 alleles showed multibranch distributions, suggestive of convergent evolution; however, all 44 iniA(H481Q) mutations were monophyletic. In conclusion, this study validates convergence analysis as a tool for identifying mutations that cause INH resistance and explores mutations in other genes. Our results suggest that embB306 mutations are likely to confer drug resistance, while iniA(H481Q) mutations are not. This approach may be applied on a genome-wide scale to identify SNPs that impact antibiotic resistance and other types of biological fitness.
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