ArticleAntimicrobial agents and chemotherapy2009
Mutations at embB codon 306 are an important molecular indicator of ethambutol resistance in Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2014Pooled it
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- Different Contributions ofInfection and drug resistance · 2024Article
- How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?Current pharmaceutical biotechnology · 2024Review
- Drug resistantPeerJ · 2022Article
- Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall.Cell surface (Amsterdam, Netherlands) · 2020Review
- Frequency of Codon 306 Mutations inInternational journal of preventive medicine · 2020Review
- Evaluation of Whole-Genome Sequence Method to Diagnose Resistance of 13 Anti-tuberculosis Drugs and Characterize Resistance Genes in Clinical Multi-Drug ResistanceFrontiers in microbiology · 2019Article
- Molecular epidemiology of tuberculosis in Tasmania and genomic characterisation of its first known multi-drug resistant case.PloS one · 2018Article
- Draft Genome Sequence of the First Confirmed Isolate of Multidrug-ResistantGenome announcements · 2017Article
- Comparative Genomic Analysis of Two Clonally Related Multidrug ResistantFrontiers in cellular and infection microbiology · 2017Article
- An application of competitive reporter monitored amplification (CMA) for rapid detection of single nucleotide polymorphisms (SNPs).PloS one · 2017Article
- Association between embB Codon 306 Mutations, Phenotypic Resistance Profiles, and Genotypic Characterization in Clinical Mycobacterium tuberculosis Isolates from Hebei, China.Antimicrobial agents and chemotherapy · 2016Article
- Geographic Differences in the Contribution of ubiA Mutations to High-Level Ethambutol Resistance in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2016Article
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Abstract
Ethambutol resistance in clinical Mycobacterium tuberculosis isolates is associated primarily with missense mutations in the embB gene. However, recent reports have described the presence of embB mutations, especially those at embB codon 306, in isolates susceptible to ethambutol. To clarify the role of embB mutations in ethambutol resistance, we sequenced the ethambutol resistance-determining region in spontaneous ethambutol-resistant mutants. In our study, 66% of spontaneous mutants contained a single point mutation in embB, with 55% of these occurring at embB 306. The MIC of ethambutol for spontaneous mutants was increased two- to eightfold relative to the pansusceptible M. tuberculosis strains from which the mutants were generated. To further characterize the role of embB 306 mutations, we directly introduced mutant alleles, embB(M306V) or embB(M306I), into pansusceptible M. tuberculosis strains and conversely reverted mutant alleles in spontaneous ethambutol-resistant mutants back to those of the wild type via allelic exchange using specialized linkage transduction. We determined that the MIC of ethambutol was reduced fourfold for three of the four spontaneous ethambutol-resistant embB 306 mutants when the mutant allele was replaced with the wild-type embB allele. The MIC for one of the spontaneous mutants genetically reverted to wild-type embB was reduced by only twofold. When the wild-type embB allele was converted to the mutant allele embB(M306V), the ethambutol MIC was increased fourfold, and when the allele was changed to M306I, the ethambutol MIC increased twofold. Our data indicate that embB 306 mutations are sufficient to confer ethambutol resistance, and detection of these mutations should be considered in the development of rapid molecular tests.
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