| Accession | ARO:3007661 |
| CARD Short Name | Mtub_ddn_MULT |
| Definition | ddn is a protein-coding gene involved in the bioreductive activation of bicyclic 4-nitroimidazole prodrugs such as PA-824 and delamanid developed for anti-tuberculosis therapy against both replicating and persistent bacteria. |
| AMR Gene Family | antibiotic resistant Mycobacterium tuberculosis nitroreductase |
| Drug Class | nitroimidazole antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Classification | 8 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + nitroimidazole antibiotic [Drug Class] + antibiotic resistant gene variant or mutant |
| Parent Term(s) | 3 ontology terms | Show + confers_resistance_to_antibiotic delamanid [Antibiotic] + confers_resistance_to_antibiotic pretomanid [Antibiotic] + antibiotic resistant Mycobacterium tuberculosis nitroreductase [AMR Gene Family] |
| Publications | Mansjö M, et al. 2022. Antimicrob Agents Chemother 66(12):e0102622 The ddn Trp20Stop Mutation and Its Association with Lineage 4.5 and Resistance to Delamanid and Pretomanid in Mycobacterium tuberculosis. (PMID 36409105) The CRyPTIC Consortium 2022. PLoS Biol 20(8):e3001721 A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. (PMID 35944069) World Health Organization. 2023. ISBN 978-92-4-008241-0. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. Second Edition. (ISBN 978-92-4-008241-0) |
Prevalence of Mycobacterium tuberculosis ddn mutation conferring resistance to nitroimidazole antibiotics among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| No prevalence data | |||||
Model Type: protein variant model
Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.
Bit-score Cut-off (blastP): 275
PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).| Mutation | Mutation type | PubMed | ReSeqTB | CRyPTIC | WHO |
|---|---|---|---|---|---|
| M1Var | single resistance variant | no data | no data | no data | WHO-R |
| W20Ter | nonsense mutation | PMID:36409105 | no data | no data | WHO-R |
| L49P | single resistance variant | no data | no data | no data | WHO-R |
| W88Ter | nonsense mutation | no data | no data | no data | WHO-R |
| W139Ter | nonsense mutation | no data | no data | no data | WHO-R |
| Curator | Description | Most Recent Edit |
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