ArticleAntimicrobial agents and chemotherapy2010
Allelic exchange and mutant selection demonstrate that common clinical embCAB gene mutations only modestly increase resistance to ethambutol in Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Diagnostic accuracy of a molecular drug susceptibility testing method for the antituberculosis drug ethambutol: a systematic review and meta-analysis.Journal of clinical microbiology · 2014Pooled 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
- The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China.BMC microbiology · 2025Article
- Mutations inAntibiotics (Basel, Switzerland) · 2024Article
- Different Contributions ofInfection and drug resistance · 2024Article
- Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics ofInfection and drug resistance · 2023Article
- Article
- Antibiotics and resistance: the two-sided coin of the mycobacterial cell wall.Cell surface (Amsterdam, Netherlands) · 2020Review
- Rapidly Correcting Frameshift Mutations in the Mycobacterium tuberculosisAntimicrobial agents and chemotherapy · 2020Article
- A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis.Scientific reports · 2019Article
- Occurrence of disputed rpoB mutations among Mycobacterium tuberculosis isolates phenotypically susceptible to rifampicin in a country with a low incidence of multidrug-resistant tuberculosis.BMC infectious diseases · 2019Article
- Comparison of Quantamatrix Multiplexed Assay Platform and GenoType MTBDR Assay Using Smear-Positive Sputum Specimens From Patients With Multidrug- Resistant/Extensively Drug-Resistant Tuberculosis in South Korea.Frontiers in microbiology · 2019Article
- Multi- and Extensively Drug Resistant Mycobacterium tuberculosis in South Africa: a Molecular Analysis of Historical Isolates.Journal of clinical microbiology · 2018Article
- Evaluation of Genotype MTBDRFrontiers in microbiology · 2018Article
- Geographic Differences in the Contribution of ubiA Mutations to High-Level Ethambutol Resistance in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2016Article
- Molecular Analysis of the embCAB Locus and embR Gene Involved in Ethambutol Resistance in Clinical Isolates of Mycobacterium tuberculosis in France.Antimicrobial agents and chemotherapy · 2015Article
- Rapid Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates Directly from Clinical Samples.Journal of clinical microbiology · 2015Article
- Analysis of embCAB mutations associated with ethambutol resistance in multidrug-resistant mycobacterium tuberculosis isolates from China.Antimicrobial agents and chemotherapy · 2015Article
- Article
- Mutations Found in embCAB, embR, and ubiA Genes of Ethambutol-Sensitive and -Resistant Mycobacterium tuberculosis Clinical Isolates from China.BioMed research international · 2015Article
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6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations within codon 306 of the Mycobacterium tuberculosis embB gene modestly increase ethambutol (EMB) MICs. To identify other causes of EMB resistance and to identify causes of high-level resistance, we generated EMB-resistant M. tuberculosis isolates in vitro and performed allelic exchange studies of embB codon 406 (embB406) and embB497 mutations. In vitro selection produced mutations already identified clinically in embB306, embB397, embB497, embB1024, and embC13, which result in EMB MICs of 8 or 14 microg/ml, 5 microg/ml, 12 microg/ml, 3 microg/ml, and 4 microg/ml, respectively, and mutations at embB320, embB324, and embB445, which have not been identified in clinical M. tuberculosis isolates and which result in EMB MICs of 8 microg/ml, 8 microg/ml, and 2 to 8 microg/ml, respectively. To definitively identify the effect of the common clinical embB497 and embB406 mutations on EMB susceptibility, we created a series of isogenic mutants, exchanging the wild-type embB497 CAG codon in EMB-susceptible M. tuberculosis strain 210 for the embB497 CGG codon and the wild-type embB406 GGC codon for either the embB406 GCC, embB406 TGC, embB406 TCC, or embB406 GAC codon. These new mutants showed 6-fold and 3- to 3.5-fold increases in the EMB MICs, respectively. In contrast to the embB306 mutants, the isogenic embB497 and embB406 mutants did not have preferential growth in the presence of isoniazid or rifampin (rifampicin) at their MICs. These results demonstrate that individual embCAB mutations confer low to moderate increases in EMB MICs. Discrepancies between the EMB MICs of laboratory mutants and clinical M. tuberculosis strains with identical mutations suggest that clinical EMB resistance is multigenic and that high-level EMB resistance requires mutations in currently unknown loci.
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