ArticleScientific reports2023
Large-scale genomic analysis of Mycobacterium tuberculosis reveals extent of target and compensatory mutations linked to multi-drug resistant tuberculosis.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 25 citations in OpenAlex.
- Melting temperature signatures reveal occasional misclassification of low-level isoniazid resistance by Xpert MTB/XDR.Microbiology spectrum · 2026Article
- Synthesis, Characterization, and Inhibitory Potential of Fagonia arabica L. Phytochemicals Coated Gold Nanoparticles Against Drug-Resistant Mycobacterium tuberculosis.Chemistry & biodiversity · 2026Article
- The Impact of HIV Viral Suppression and Immune Status on Rifampicin-Resistant Tuberculosis Outcomes: A Systematic Review and Meta-Analysis Protocol.Tropical medicine and infectious disease · 2026Review
- Routine Molecular Surveillance of Drug-Resistant Tuberculosis: Translating Mutation Proxies into Clinical Governance Intelligence in Rural Eastern Cape.Healthcare (Basel, Switzerland) · 2026Article
- Genetic Characterization of First-Line Drug-Resistance Mutations in Multidrug-ResistantPathogens (Basel, Switzerland) · 2026Article
- The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis.Nature communications · 2026Article
- Multicentre field evaluation of Xpert MTB/XDR in sub-Saharan Africa.ERJ open research · 2026Article
- Phenotypic drug resistance and genome sequencing based identified mutations linked to resistance in Mycobacterium tuberculosis isolated from extrapulmonary clinical specimens.Scientific reports · 2026Article
- Extensive Endemic Transmission of Multidrug-ResistantOpen forum infectious diseases · 2026Article
- Machine learning-based analysis of drug resistance mutations in Mycobacterium tuberculosis.PloS one · 2026Article
- Genomic landscape ofNew microbes and new infections · 2025Article
- Genomic characterization of XDR Mycobacterium tuberculosis isolates in Argentina (2006-2015).BMC infectious diseases · 2025Article
- TheAntimicrobial agents and chemotherapy · 2025Article
- Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China.Frontiers in public health · 2025Article
- Article
- Catalase-peroxidase (KatG): a potential frontier in tuberculosis drug development.Critical reviews in biochemistry and molecular biology · 2024Review
- Combating antimicrobial resistance in malaria, HIV and tuberculosis.Nature reviews. Drug discovery · 2024Review
- Large-scale statistical analysis of Mycobacterium tuberculosis genome sequences identifies compensatory mutations associated with multi-drug resistance.Scientific reports · 2024Article
- Compensatory mutations are associated with increasedMicrobial genomics · 2024Article
- Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.Microbiology spectrum · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to isoniazid (INH) and rifampicin (RIF) first-line drugs in Mycobacterium tuberculosis (Mtb), together called multi-drug resistance, threatens tuberculosis control. Resistance mutations in katG (for INH) and rpoB (RIF) genes often come with fitness costs. To overcome these costs, Mtb compensatory mutations have arisen in rpoC/rpoA (RIF) and ahpC (INH) loci. By leveraging the presence of known compensatory mutations, we aimed to detect novel resistance mutations occurring in INH and RIF target genes. Across ~ 32 k Mtb isolates with whole genome sequencing (WGS) data, there were 6262 (35.7%) with INH and 5435 (30.7%) with RIF phenotypic resistance. Known mutations in katG and rpoB explained ~ 99% of resistance. However, 188 (0.6%) isolates had ahpC compensatory mutations with no known resistance mutations in katG, leading to the identification of 31 putative resistance mutations in katG, each observed in at least 3 isolates. These putative katG mutations can co-occur with other INH variants (e.g., katG-Ser315Thr, fabG1 mutations). For RIF, there were no isolates with rpoC/rpoA compensatory mutations and unknown resistance mutations. Overall, using WGS data we identified putative resistance markers for INH that could be used for genotypic drug-resistance profiling. Establishing the complete repertoire of Mtb resistance mutations will assist the clinical management of tuberculosis.
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