ArticleThe Journal of antimicrobial chemotherapy2017
Identification of novel mutations associated with cycloserine resistance in Mycobacterium tuberculosis.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Metabolic flexibility and an unusual route for peptidoglycan muramic acid recycling in mycobacteria.The Journal of biological chemistry · 2026Article
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- A Comprehensive Review of Genetic Mechanisms ofInfection and drug resistance · 2026Review
- Mycobacterium tuberculosis uses intrinsically disordered, fast evolving proteins to interact with conserved host factors.Genome biology · 2025Article
- Solvent-Assisted Catalysis: Water Promotes Ring Closure Formation of 2‑Oxazolidinone from Amino Acid DerivedACS organic & inorganic Au · 2025Article
- Cycloserine resistance among drug-resistant tuberculosis cases in Taiwan.Microbiology spectrum · 2025Article
- High Prevalence of atpE Mutations in Bedaquiline-Resistant Mycobacterium tuberculosis Isolates, Russia.Emerging infectious diseases · 2025Article
- Feature selection and aggregation for antibiotic resistance GWAS inFrontiers in microbiology · 2025Article
- Breaking barriers: The potential of nanosystems in antituberculosis therapy.Bioactive materials · 2024Review
- Dual transcriptional inhibition of glutamate and alanine racemase is synergistic inMicrobiology (Reading, England) · 2024Article
- Metabolic Rewiring ofMetabolites · 2024Review
- Discordance Between Phenotypic and WGS-Based Drug Susceptibility Testing Results for Some Anti-Tuberculosis Drugs: A Snapshot Study of PairedInfection and drug resistance · 2024Article
- How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?Current pharmaceutical biotechnology · 2024Review
- Roles of Lipolytic enzymes inFrontiers in microbiology · 2024Review
- Gated Calcium Ion Channel and Mutation Mechanisms in Multidrug-Resistant Tuberculosis.International journal of molecular sciences · 2023Review
- Heterologous production of the D-cycloserine intermediate O-acetyl-L-serine in a human type II pulmonary cell model.Scientific reports · 2023Article
- High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistantEmerging microbes & infections · 2022Article
- Genome-Wide Study of Drug ResistantMicroorganisms · 2022Article
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Authors and funding
6 authors.
Funding
Abstract
objectivesd-Cycloserine is an important second-line drug used to treat MDR- and XDR-TB. However, the mechanisms of resistance to d-cycloserine are not well understood. Here we investigated the molecular basis of d-cycloserine resistance using in vitro-isolated resistant mutants.
methodsMycobacterium tuberculosis H37Rv was subjected to mutant selection on 7H11 agar plates containing varying concentrations of d-cycloserine. A total of 18 d-cycloserine-resistant mutants were isolated and subjected to WGS. The identified mutations associated with d-cycloserine resistance were confirmed by PCR and Sanger sequencing.
resultsWe identified mutations in 16 genes that are associated with d-cycloserine resistance. Interestingly, we found mutations only in alr (rv3423c) encoding alanine racemase, but not in other known d-cycloserine resistance-associated genes such as ddl, cycA or ald. Instead, we identified 13 new genes [rv0059, betP (rv0917), rv0221, rv1403c, rv1683, rv1726, gabD2 (rv1731), rv2749, sugI (rv3331), hisC2 (rv3772), the 5' intergenic region of rv3345c and rv1435c, and the 3' region of rv0759c] that had solo mutations associated with d-cycloserine resistance. Our findings indicate that the mechanisms of d-cycloserine resistance are more complex than previously thought and involve genes participating in different cellular functions such as lipid metabolism, methyltransferase, the stress response and transport systems.
conclusionsNew mutations in diverse genes associated with d-cycloserine resistance have been identified that shed new light on the mechanisms of action and resistance of d-cycloserine. Future studies are needed to verify these findings in clinical strains so that molecular detection of d-cycloserine resistance for improved treatment of MDR-TB can be developed.
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