ArticleGenome medicine2020
Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex.
Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 86 citations in OpenAlex.
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- Characteristics of compensatory mutations in rifampicin-resistant tuberculosis and their association with compensated transmission in Ningbo, China.BMC microbiology · 2025Article
- Mycobacterium tuberculosis complex Lineage 1: A neglected cause of tuberculosis.PLoS neglected tropical diseases · 2025Review
- Antibiotic tolerance & resilience in M. tuberculosis: Potential to predict & pre-empt antibiotic resistance.The Indian journal of medical research · 2025Article
- Harnessing essential oils for sustainable food preservatives: Chemical composition, mechanisms, applications, and safety insights.Food chemistry: X · 2025Review
- An improved catalogue for whole-genome sequencing prediction of bedaquiline resistance inMicrobial genomics · 2025Article
- Multivariable regression models improve accuracy and sensitive grading of antibiotic resistance mutations in Mycobacterium tuberculosis.Nature communications · 2025Article
- Clinical epidemiology, genetic diversity, and drug susceptibility patterns by whole genome sequencing ofIJID regions · 2025Article
- A pragmatic pipeline for drug resistance and lineage identification in Mycobacterium tuberculosis using whole genome sequencing.PLOS global public health · 2025Article
- Whole genome sequence ofFrontiers in microbiology · 2025Article
- Widespread loss-of-function mutations implicating preexisting resistance to new or repurposed anti-tuberculosis drugs.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains.The Lancet. Microbe · 2024Article
- Drug susceptibility testing and line probe assay of first-line anti-tuberculosis drugs among presumptive tuberculosis patients attending a secondary care hospital in Bhubaneswar.Journal of family medicine and primary care · 2024Article
- The exceptions that prove the rule-a historical view of bedaquiline susceptibility.Genome medicine · 2024Article
- Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone.Microbiology spectrum · 2024Article
- Refined understanding of the impact of theMicrobiology spectrum · 2024Article
- Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis.Genome medicine · 2024Article
- Loss-of-function mutations inAntimicrobial agents and chemotherapy · 2024Article
- Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing: From Sequence Data to Resistance Profiles.Methods in molecular biology (Clifton, N.J.) · 2024Article
Corrections and comments
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Authors and funding
16 authors at 11 institutions in 3 countries.
Funding
Abstract
backgroundA comprehensive understanding of the pre-existing genetic variation in genes associated with antibiotic resistance in the Mycobacterium tuberculosis complex (MTBC) is needed to accurately interpret whole-genome sequencing data for genotypic drug susceptibility testing (DST).
methodsWe investigated mutations in 92 genes implicated in resistance to 21 anti-tuberculosis drugs using the genomes of 405 phylogenetically diverse MTBC strains. The role of phylogenetically informative mutations was assessed by routine phenotypic DST data for the first-line drugs isoniazid, rifampicin, ethambutol, and pyrazinamide from a separate collection of over 7000 clinical strains. Selected mutations/strains were further investigated by minimum inhibitory concentration (MIC) testing.
resultsOut of 547 phylogenetically informative mutations identified, 138 were classified as not correlating with resistance to first-line drugs. MIC testing did not reveal a discernible impact of a Rv1979c deletion shared by M. africanum lineage 5 strains on resistance to clofazimine. Finally, we found molecular evidence that some MTBC subgroups may be hyper-susceptible to bedaquiline and clofazimine by different loss-of-function mutations affecting a drug efflux pump subunit (MmpL5).
conclusionsOur findings underline that the genetic diversity in MTBC has to be studied more systematically to inform the design of clinical trials and to define sound epidemiologic cut-off values (ECOFFs) for new and repurposed anti-tuberculosis drugs. In that regard, our comprehensive variant catalogue provides a solid basis for the interpretation of mutations in genotypic as well as in phenotypic DST assays.
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