ArticleEmerging microbes & infections2015
Novel katG mutations causing isoniazid resistance in clinical M. tuberculosis isolates.
Article in Emerging microbes & infections, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis.The Lancet. Infectious diseases · 2024Pooled it
- Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Uncovering the structural impact of KatG Ser315 mutations in Mycobacterium tuberculosis via cryo-EM.Protein science : a publication of the Protein Society · 2026Article
- Isoniazid potentiates tigecycline to kill methicillin-resistantEmerging microbes & infections · 2025Article
- Application of engineered CRISPR/Cas12a variants with altered protospacer adjacent motif specificities for the detection of isoniazid resistance mutations inMicrobiology spectrum · 2025Article
- Is Mycobacterial InhA a Suitable Target for Rational Drug Design?ChemMedChem · 2025Review
- Genetic mechanisms of co-emergence of INH-resistantMicrobiology spectrum · 2024Article
- Identification ofInfection and drug resistance · 2024Review
- The performance of Xpert MTB/RIF and MTBDRplus within a Programmatic setting at TB Laboratory in Rio de Janeiro, Brazil.Revista da Sociedade Brasileira de Medicina Tropical · 2024Article
- Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Experiences from 4 Years of Organization of an External Quality Assessment for Mycobacterium tuberculosis Whole-Genome Sequencing in the European Union/European Economic Area.Microbiology spectrum · 2023Article
- Large-scale genomic analysis of Mycobacterium tuberculosis reveals extent of target and compensatory mutations linked to multi-drug resistant tuberculosis.Scientific reports · 2023Article
- Novel and reported compensatory mutations inFrontiers in microbiology · 2023Article
- Genetic Characterization Conferred Co-Resistance to Isoniazid and Ethionamide inInfection and drug resistance · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Ultrasensitive Detection of Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- Phylogenetic lineages of tuberculosis isolates and their association with patient demographics in Tanzania.BMC genomics · 2022Article
- Detection and characterization of mutations in genes related to isoniazid resistance in Mycobacterium tuberculosis clinical isolates from Iran.Molecular biology reports · 2022Article
- Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study.Antimicrobial agents and chemotherapy · 2022Article
- RETRACTED: An Overview of Antimicrobial Stewardship Optimization: The Use of Antibiotics in Humans and Animals to Prevent Resistance.Antibiotics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
We report the discovery and confirmation of 23 novel mutations with previously undocumented role in isoniazid (INH) drug resistance, in catalase-peroxidase (katG) gene of Mycobacterium tuberculosis (Mtb) isolates. With these mutations, a synonymous mutation in fabG1 (g609a), and two canonical mutations, we were able to explain 98% of the phenotypic resistance observed in 366 clinical Mtb isolates collected from four high tuberculosis (TB)-burden countries: India, Moldova, Philippines, and South Africa. We conducted overlapping targeted and whole-genome sequencing for variant discovery in all clinical isolates with a variety of INH-resistant phenotypes. Our analysis showed that just two canonical mutations (katG 315AGC-ACC and inhA promoter-15C-T) identified 89.5% of resistance phenotypes in our collection. Inclusion of the 23 novel mutations reported here, and the previously documented point mutation in fabG1, increased the sensitivity of these mutations as markers of INH resistance to 98%. Only six (2%) of the 332 resistant isolates in our collection did not harbor one or more of these mutations. The third most prevalent substitution, at inhA promoter position -8, present in 39 resistant isolates, was of no diagnostic significance since it always co-occurred with katG 315. 79% of our isolates harboring novel mutations belong to genetic group 1 indicating a higher tendency for this group to go down an uncommon evolutionary path and evade molecular diagnostics. The results of this study contribute to our understanding of the mechanisms of INH resistance in Mtb isolates that lack the canonical mutations and could improve the sensitivity of next generation molecular diagnostics.
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