ArticleThe Journal of antimicrobial chemotherapy2015
Identification of novel mutations associated with clofazimine resistance in Mycobacterium tuberculosis.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 166 citations in OpenAlex.
- Genetic variants and their association with phenotypic resistance to bedaquiline inThe Lancet. Microbe · 2021Pooled it
- Systematic review of mutations associated with resistance to the new and repurposed Mycobacterium tuberculosis drugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid.The Journal of antimicrobial chemotherapy · 2020Pooled it
- ComparativeMicrobiology spectrum · 2026Article
- Review
- Rapid Identification of Drug-Resistant Tuberculosis Using Nanopore Targeted Next-Generation Sequencing from Sputum and Culture Isolates: Accuracy and Limitations.Infection and drug resistance · 2026Article
- Examination of Genetic Mutations of Clofazimine Resistance in Drug-Resistant Mycobacterium TB Isolates.Current microbiology · 2025Article
- Vitamin C potentiates the killing ofmBio · 2025Article
- Novel mutations in theAntimicrobial agents and chemotherapy · 2025Article
- Unraveling Drug Resistance inInternational journal of microbiology · 2025Review
- 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
- Micro-nanoemulsion and nanoparticle-assisted drug delivery against drug-resistant tuberculosis: recent developments.Clinical microbiology reviews · 2023Review
- Designing molecular diagnostics for current tuberculosis drug regimens.Emerging microbes & infections · 2023Article
- Clustering minimal inhibitory concentration data through Bayesian mixture models: An application to detectStatistical methods in medical research · 2023Article
- Investigation of genomic mutations and their association with phenotypic resistance to new and repurposed drugs in Mycobacterium tuberculosis complex clinical isolates.The Journal of antimicrobial chemotherapy · 2023Article
- Article
- Spontaneous mutational patterns and novel mutations for bedaquiline and clofazimine resistance inMicrobiology spectrum · 2023Article
- Bedquiline Resistance Mutations: Correlations with Drug Exposures and Impact on the Proteome in M. tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Emergence of Canonical and Noncanonical Genomic Variants followingAntimicrobial agents and chemotherapy · 2023Article
- Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline againstFrontiers in medicine · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesAlthough clofazimine has been traditionally used to treat leprosy, there is recent interest in using clofazimine for the treatment of MDR-TB and drug-susceptible TB. However, the mechanisms of resistance to clofazimine are poorly understood. Here, we investigated the molecular basis of clofazimine resistance using resistant mutants isolated in vitro.
methodsWe isolated 96 mutants of Mycobacterium tuberculosis resistant to clofazimine and performed WGS and Sanger sequencing to identify possible mutations associated with clofazimine resistance.
resultsWe found that 97% (93/96) of clofazimine-resistant mutants had a mutation in rv0678 encoding a transcription repressor for efflux pump MmpL5. Two mutational hot spots at nucleotide positions 193 and 466 in rv0678 accounted for 43.8% (42/96) and 11.5% (11/96) of the mutations, respectively. The previously reported A202G mutation (S68G) in rv0678 occurred less frequently, in 5 of 96 mutants. The remaining 34 mutations were scattered along the entire rv0678 gene. We discovered two new genes (rv1979c and rv2535c) associated with clofazimine resistance in mutants without rv0678 mutations.
conclusionsMutations in rv0678 are a major mechanism of clofazimine resistance. Our findings provide useful information for the design of new molecular tests for rapid detection of clofazimine resistance. Further studies are needed to address the role of rv1979c and rv2535c in clofazimine resistance and mechanisms of action.
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