ArticleNature genetics2013
Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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111 citing papers in PubMed, 203 citations in OpenAlex.
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- Structure-Based Virtual Screening of Natural Product-Derived Inhibitors Targeting Rv3806c in the Decaprenylphosphoryl-d-Arabinose Biosynthetic Pathway ofInternational journal of molecular sciences · 2026Article
- Convolutional neural networks quantify antibiotic resistance in Mycobacterium tuberculosis with diagnostic grade accuracy and predict treatment response.Nature communications · 2026Article
- PE/PPE proteins contribute to Mycobacterium tuberculosis drug resistance.Nature communications · 2026Article
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- Identification and Evaluation of dibasic piperidines as novel cell wall inhibitors againstbioRxiv : the preprint server for biology · 2026Article
- Patterns of Drug Resistance and Treatment Outcomes in Drug-Resistant Tuberculosis Patients in Fuyang City: A Three-Year Retrospective Study.Infection and drug resistance · 2026Article
- An explainable artificial intelligence framework reveals mutations associated with drug resistance inBiosafety and health · 2025Article
- Unraveling Epistatic Interactions Between Sites Under Drug-Dependent Selection in the Mycobacterium tuberculosis Genome.Molecular biology and evolution · 2025Article
- Enhanced diagnosis of multi-drug-resistant microbes using group association modeling and machine learning.Nature communications · 2025Article
- Age-Dependent Pleomorphism inMicroorganisms · 2025Article
- Predicting Drug Resistance inDiagnostics (Basel, Switzerland) · 2025Article
- Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.Frontiers in medicine · 2025Review
- Genetic Analysis of Molecular Mechanisms of Drug Resistance inInfection and drug resistance · 2025Review
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Universal Lineage-Independent Markers of Multidrug Resistance inMicroorganisms · 2024Article
- Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis.Nature microbiology · 2024Article
- Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Evolution of Laboratory Diagnosis of Tuberculosis.Clinics and practice · 2024Review
51 more citing papers are in PubMed but not listed here.
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11 authors at 3 institutions in 1 country.
Funding
Abstract
To study the evolution of drug resistance, we genetically and biochemically characterized Mycobacterium tuberculosis strains selected in vitro for ethambutol resistance. Mutations in decaprenylphosphoryl-β-D-arabinose (DPA) biosynthetic and utilization pathway genes Rv3806c, Rv3792, embB and embC accumulated to produce a wide range of ethambutol minimal inhibitory concentrations (MICs) that depended on mutation type and number. Rv3806c mutations increased DPA synthesis, causing MICs to double from 2 to 4 μg/ml in a wild-type background and to increase from 16 to 32 μg/ml in an embB codon 306 mutant background. Synonymous mutations in Rv3792 increased the expression of downstream embC, an ethambutol target, resulting in MICs of 8 μg/ml. Multistep selection was required for high-level resistance. Mutations in embC or very high embC expression were observed at the highest resistance level. In clinical isolates, Rv3806c mutations were associated with high-level resistance and had multiplicative effects with embB mutations on MICs. Ethambutol resistance is acquired through the acquisition of mutations that interact in complex ways to produce a range of MICs, from those falling below breakpoint values to ones representing high-level resistance.
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