Mycobacterium tuberculosis ddn mutation conferring resistance to nitroimidazole antibiotics

Accession ARO:3007661
CARD Short NameMtub_ddn_MULT
Definitionddn 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 Familyantibiotic resistant Mycobacterium tuberculosis nitroreductase
Drug Classnitroimidazole antibiotic
Resistance Mechanismantibiotic target alteration
Classification8 ontology terms | Show
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)

Resistomes

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 413 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).

Prevalence: protein variant model

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
No prevalence data


Detection Models

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

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:


>gb|NP_218064.1|+|Mycobacterium tuberculosis ddn mutation conferring resistance to nitroimidazole antibiotics [Mycobacterium tuberculosis H37Rv]
MPKSPPRFLNSPLSDFFIKWMSRINTWMYRRNDGEGLGGTFQKIPVALLTTTGRKTGQPR
VNPLYFLRDGGRVIVAASKGGAEKNPMWYLNLKANPKVQVQIKKEVLDLTARDATDEERA
EYWPQLVTMYPSYQDYQSWTDRTIPIVVCEP



>gb|NC_000962.3|+|3986844-3987299|Mycobacterium tuberculosis ddn mutation conferring resistance to nitroimidazole antibiotics [Mycobacterium tuberculosis H37Rv]
ATGCCGAAATCACCGCCGCGGTTTCTGAATTCGCCGCTCAGCGACTTCTTTATCAAGTGGATGTCACGGATTAATACCTGGATGTACCGC
CGCAACGACGGGGAGGGTCTGGGCGGCACCTTCCAGAAGATTCCGGTCGCGCTGCTGACCACCACCGGCCGCAAGACCGGCCAGCCGCGG
GTCAACCCGCTCTACTTCCTGCGCGACGGTGGGCGGGTCATTGTCGCGGCCTCCAAGGGCGGCGCGGAGAAGAACCCGATGTGGTACCTC
AACCTCAAGGCCAACCCCAAGGTTCAGGTACAGATCAAAAAGGAAGTGCTGGACCTTACCGCGCGGGACGCGACCGACGAGGAGCGCGCC
GAATATTGGCCACAGTTGGTCACGATGTACCCAAGTTATCAGGACTACCAGTCCTGGACCGACCGCACGATCCCGATCGTGGTTTGCGAA
CCCTGA