ArticleScientific reports2021
Genetic diversity of candidate loci linked to Mycobacterium tuberculosis resistance to bedaquiline, delamanid and pretomanid.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Exploiting DprE2 pathway redundancy to enhance potency and overcome resistance to pretomanid in Mycobacterium tuberculosis.npj antimicrobials and resistance · 2026Article
- A Case of Transmission of Bedaquiline- and Linezolid-Resistant Tuberculosis.International journal of molecular sciences · 2026Article
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- Whole-Genome Sequencing and Phenotypic Drug Susceptibility Testing of Bedaquilin, Delamanid, Pretomanid, and Linezolid in Drug-ResistantPathogens (Basel, Switzerland) · 2026Article
- Profiling of BDQ-induced transcriptome suggests amino acid metabolism and stress responses as alternate mechanisms contributing to BDQ tolerance inMicrobiology spectrum · 2026Article
- The urgency to include palliative care in the response to tuberculosis in Brazil.Cadernos de saude publica · 2026Article
- Whole genome sequencing-based detection of extensively drug-resistant tuberculosis from Ethiopia.Communications medicine · 2025Article
- Pretomanid for the treatment of drug resistant pulmonary tuberculosis: a comprehensive review.Archives of microbiology · 2025Review
- Molecular resistance mechanisms to newly approved antibiotics (2017-2025) in WHO priority pathogens.Frontiers in microbiology · 2025Review
- The microevolutionary trajectory of endemic multidrug-resistant tuberculosis strains in Portugal toward increased drug resistance levels and its clinical significance.Frontiers 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
- Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing.BMC genomics · 2024Article
- Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China.Annals of clinical microbiology and antimicrobials · 2024Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Metabolic Rewiring ofMetabolites · 2024Review
- Loss-of-function mutations inAntimicrobial agents and chemotherapy · 2024Article
- 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
- Novel Derivatives of Quinoxaline-2-carboxylic Acid 1,4-Dioxides as Antimycobacterial Agents: Mechanistic Studies and Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions.The Journal of clinical investigation · 2023Review
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Authors and funding
12 authors.
Funding
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases worldwide. Multidrug and extensively drug-resistant strains are making disease control difficult, and exhausting treatment options. New anti-TB drugs bedaquiline (BDQ), delamanid (DLM) and pretomanid (PTM) have been approved for the treatment of multi-drug resistant TB, but there is increasing resistance to them. Nine genetic loci strongly linked to resistance have been identified (mmpR5, atpE, and pepQ for BDQ; ddn, fgd1, fbiA, fbiB, fbiC, and fbiD for DLM/PTM). Here we investigated the genetic diversity of these loci across >33,000 M. tuberculosis isolates. In addition, epistatic mutations in mmpL5-mmpS5 as well as variants in ndh, implicated for DLM/PTM resistance in M. smegmatis, were explored. Our analysis revealed 1,227 variants across the nine genes, with the majority (78%) present in isolates collected prior to the roll-out of BDQ and DLM/PTM. We identified phylogenetically-related mutations, which are unlikely to be resistance associated, but also high-impact variants such as frameshifts (e.g. in mmpR5, ddn) with likely functional effects, as well as non-synonymous mutations predominantly in MDR-/XDR-TB strains with predicted protein destabilising effects. Overall, our work provides a comprehensive mutational catalogue for BDQ and DLM/PTM associated genes, which will assist with establishing associations with phenotypic resistance; thereby, improving the understanding of the causative mechanisms of resistance for these drugs, leading to better treatment outcomes.
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