ArticleAntimicrobial agents and chemotherapy2014
Mutations in the embC-embA intergenic region contribute to Mycobacterium tuberculosis resistance to ethambutol.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 43 citations in OpenAlex.
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- Whole-genome sequencing analysis to identify antimicrobial resistance regions and virulence factors in Mycobacterium tuberculosis isolates from the Amhara Region, Ethiopia.Scientific reports · 2025Article
- The implications of mutations in multiple genes associated with ethambutol resistance among multidrug-resistant tuberculosis isolates from China.BMC microbiology · 2025Article
- Predicting Drug Resistance inDiagnostics (Basel, Switzerland) · 2025Article
- The microevolutionary trajectory of endemic multidrug-resistant tuberculosis strains in Portugal toward increased drug resistance levels and its clinical significance.Frontiers in microbiology · 2025Article
- Machine learning-based prediction of antibiotic resistance in Mycobacterium tuberculosis clinical isolates from Uganda.BMC infectious diseases · 2024Article
- A dose-response model for statistical analysis of chemical genetic interactions in CRISPRi screens.PLoS computational biology · 2024Article
- Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection.Biomolecules · 2023Review
- Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan.Scientific reports · 2023Article
- Omics analysis of Mycobacterium tuberculosis isolates uncovers Rv3094c, an ethionamide metabolism-associated gene.Communications biology · 2023Article
- Mutations and insights into the molecular mechanisms of resistance of Mycobacterium tuberculosis to first-line.Genetics and molecular biology · 2023Article
- Functional analysis of intergenic regulatory regions of genes encoding surface adhesins inBiofilm · 2022Article
- Experimental Polymorphism Survey in Intergenic Regions of theMicroorganisms · 2022Article
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- Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection.EMBO reports · 2021Article
- Correlation of drug resistance with single nucleotide variations through genome analysis and experimental validation in a multi-drug resistant clinical isolate of M. tuberculosis.BMC microbiology · 2020Article
- Detecting Ethambutol Resistance inFrontiers in microbiology · 2020Article
- Within-Host Adaptation Mediated by Intergenic Evolution in Pseudomonas aeruginosa.Genome biology and evolution · 2019Article
- A deletion in the RD105 region confers resistance to multiple drugs in Mycobacterium tuberculosis.BMC biology · 2019Article
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7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The rapid increase in Mycobacterium tuberculosis resistance to ethambutol (EMB) threatens the diagnosis and treatment of tuberculosis (TB). We investigated the role of mutations in the embC-embA intergenic region (IGR) in EMB-resistant clinical strains from east China. A total of 767 M. tuberculosis clinical strains were collected and analyzed for their drug susceptibility to EMB using the MGIT 960 system and MIC assay, and the embC-embA IGRs of these strains were sequenced. The transcriptional activity of the embC-embA IGR mutations was examined by reporter gene assays in recombinant Mycobacterium smegmatis strains, and the effect of IGR mutations on its binding to EmbR, a transcription regulator of embAB, was analyzed by gel mobility shift assays. Correlation coefficient analysis showed that the embC-embA IGR mutation is associated with EMB resistance. The clinical strains carrying IGR mutations had a much higher level of embA and embB mRNA as well as higher MICs to EMB. IGR mutations had higher transcriptional activity when transformed into M. smegmatis strains. Mutated IGRs bound to EmbR with much higher affinity than wild-type fragments. The sensitivity of molecular drug susceptibility testing (DST) with IGR mutations as an additional marker increased from 65.5% to 73.5%. Mutations of the embC-embA IGR enhance the binding of EmbR to the promoter region of embAB and increase the expression of embAB, thus contributing to EMB resistance. Therefore, identification of IGR mutations as markers of EMB resistance could increase the sensitivity of molecular DST.
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