ArticleBMC microbiology2022
Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ naïve TB patients in Pakistan.
Article in BMC microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global mapping of bedaquiline-resistant Mycobacterium tuberculosis: a systematic review.BMC infectious diseases · 2026Pooled it
- Tuberculosis transmission and resistance among Ukrainian migrants and its impact on multidrug-resistant tuberculosis dynamics in high-influx host countries.BMC microbiology · 2026Article
- Acquisition of bedaquiline and clofazimine resistance in association with a novel loss-of-function mutation in theASM case reports · 2026Article
- Profiling of BDQ-induced transcriptome suggests amino acid metabolism and stress responses as alternate mechanisms contributing to BDQ tolerance inMicrobiology spectrum · 2026Article
- Bedaquiline resistance-associated genetic mutations and minimum inhibitory concentrations in drug-resistant tuberculosis clinical isolates from Limpopo province, South Africa.Frontiers in microbiology · 2026Article
- Netupitant Exhibits Potent Activity onACS infectious diseases · 2025Article
- Clinical best practices for caring for people with expanded resistance to newer TB drugs.IJTLD open · 2025Review
- Structure and assembly of the MmpL5/MmpS5 efflux transporter from Mycobacterium tuberculosis.Nature communications · 2025Article
- Structure and mechanism of a mycobacterial isoniazid efflux pump MsRv1273c/72c with a degenerate nucleotide-binding site.Nature communications · 2025Article
- Investigation of bedaquiline heteroresistance amongMicrobiology spectrum · 2025Article
- Innovative Bedaquiline-Based Delivery Systems for Multidrug-Resistant Tuberculosis Treatment.Infectious disorders drug targets · 2025Review
- Leveraging large-scale Mycobacterium tuberculosis whole genome sequence data to characterise drug-resistant mutations using machine learning and statistical approaches.Scientific reports · 2024Article
- Breaking barriers: The potential of nanosystems in antituberculosis therapy.Bioactive materials · 2024Review
- EfpA is required for regrowth ofAntimicrobial agents and chemotherapy · 2024Article
- Identification of genetic determinants of bedaquiline resistance inMicrobiology spectrum · 2024Article
- Identification ofInfection and drug resistance · 2024Review
- Intricate link between siderophore secretion and drug efflux inAntimicrobial agents and chemotherapy · 2023Article
- Spontaneous mutational patterns and novel mutations for bedaquiline and clofazimine resistance inMicrobiology spectrum · 2023Article
- Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline againstFrontiers in medicine · 2023Review
- In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis.Infection and drug resistance · 2023Article
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11 authors.
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Abstract
backgroundMutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
methodsBased on convenience sampling, we studied 48 MTB clinical isolates from BDQ naïve TB patients. These isolates (from our strain bank) included 38 MDR/pre-XDR/XDR (10 BDQ resistant, 8 BDQ intermediate and 20 BDQ susceptible) and 10 pan drug susceptible MTB isolates. All strains were subjected to whole genome sequencing and genomes were analysed to identify variants in Rv0678, pepQ, atpE, Rv1979c, mmpLS and mmpL5 and drug resistance associated efflux pump genes.
resultsOf the BDQ resistant and intermediate strains 44% (8/18) had variants in Rv0678 including; two reported mutations S63R/G, six previously unreported variants; L40F, R50Q and R107C and three frameshift mutations; G25fs, D64fs and D109fs. Variants in efflux pumps; Rv1273c (G462K), Rv0507c (R426H) and Rv1634c (E198R) were found to be present in drug resistant isolates including BDQ resistant and intermediate isolates. E198R in efflux pump gene Rv1634c was the most frequently occurring variant in BDQ resistant and intermediate isolates (n = 10).
conclusionWe found RAVs in Rv0678 to be commonly associated with BDQ resistance. Further confirmation of the role of variants in efflux pump genes in resistance is required so that they may be incorporated in genome-based diagnostics for drug resistant MTB.
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