ArticleJournal of clinical microbiology2017
Emergence of mmpT5 Variants during Bedaquiline Treatment of Mycobacterium intracellulare Lung Disease.
Article in Journal of clinical microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis.The Journal of antimicrobial chemotherapy · 2024Pooled it
- Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study.Journal of clinical pharmacology · 2021Trial
- Current Perspectives onInternational journal of molecular sciences · 2026Review
- Genetic analysis ofiScience · 2026Article
- Nintedanib Enhances the Antibacterial Activity of Bedaquiline Against Non-Tuberculous Mycobacteria: In vitro and in Mice Models.Infection and drug resistance · 2026Article
- Bedaquiline Resistance: A Looming Global Threat in Tuberculosis Management.Current microbiology · 2025Review
- Comparative Analysis of Evolutionary Distances Using the GenusInternational journal of molecular sciences · 2025Article
- The acetyltransferase CysE modulates virulence and drug resistance of Mycobacterium tuberculosis by interfering with oxidative stress responses.Communications biology · 2025Article
- Bedaquiline combined with clofazimine as salvage therapy for 11 patients with nontuberculous mycobacterial lung disease.BMC infectious diseases · 2025Article
- Bedaquiline does not enhance a clofazimine-azithromycin-ethambutol regimen againstAntimicrobial agents and chemotherapy · 2025Article
- GrcC1 mediates low-level resistance to multiple drugs inMicrobiology spectrum · 2025Article
- Dinucleotide codon substitutions as a signature of diversifying selection inFrontiers in molecular biosciences · 2025Article
- Mycobactin and clofazimine activity are negatively correlated in mycobacteria.Frontiers in microbiology · 2025Article
- Recent advances in immunopathogenesis and clinical practice: mastering the challenge-managing of non-tuberculous mycobacteria.Frontiers in immunology · 2025Review
- Review
- The structure of Mycobacterium thermoresistibile MmpS5 reveals a conserved disulfide bond across mycobacteria.Metallomics : integrated biometal science · 2024Article
- Sources, transmission and hospital-associated outbreaks of nontuberculous mycobacteria: a review.Future microbiology · 2024Review
- Exploring antibiotic resistance mechanisms inFrontiers in microbiology · 2024Review
- Drug susceptibility distributions ofAntimicrobial agents and chemotherapy · 2023Article
- A Comprehensive Overview of the Antibiotics Approved in the Last Two Decades: Retrospects and Prospects.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bedaquiline (BDQ), a diarylquinoline antibiotic that targets ATP synthase, is effective for the treatment of Mycobacterium tuberculosis infections that no longer respond to conventional drugs. While investigating the off-label use of BDQ as salvage therapy, seven of 13 patients with Mycobacterium intracellulare lung disease had an initial microbiological response and then relapsed. Whole-genome comparison of pretreatment and relapse isolates of M. intracellulare uncovered mutations in a previously uncharacterized locus, mmpT5 Preliminary analysis suggested similarities between mmpT5 and the mmpR5 locus, which is associated with low-level BDQ resistance in M. tuberculosis Both genes encode transcriptional regulators and are adjacent to orthologs of the mmpS5-mmpL5 drug efflux operon. However, MmpT5 belongs to the TetR superfamily, whereas MmpR5 is a MarR family protein. Targeted sequencing uncovered nonsynonymous mmpT5 mutations in isolates from all seven relapse cases, including two pretreatment isolates. In contrast, only two relapse patient isolates had nonsynonymous changes in ATP synthase subunit c (atpE), the primary target of BDQ. Susceptibility testing indicated that mmpT5 mutations are associated with modest 2- to 8-fold increases in MICs for BDQ and clofazimine, whereas one atpE mutant exhibited a 50-fold increase in MIC for BDQ. Bedaquiline shows potential for the treatment of M. intracellulare lung disease, but optimization of treatment regimens is required to prevent the emergence of mmpT5 variants and microbiological relapse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.