| Accession | ARO:3003461 |
| Synonym(s) | Rv1854c |
| CARD Short Name | Mtub_ndh_INH |
| Definition | Point mutations in the Mycobacterium tuberculosis ndh gene shown clinically to confer resistance to isoniazid. |
| AMR Gene Family | antibiotic resistant ndh |
| Drug Class | isoniazid-like antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium tuberculosisg+wgs |
| 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 + isoniazid-like antibiotic [Drug Class] + antibiotic resistant gene variant or mutant |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic isoniazid [Antibiotic] + antibiotic resistant ndh [AMR Gene Family] |
| Publications | Cardoso RF, et al. 2007. Mem Inst Oswaldo Cruz 102(1): 59-61. Characterization of ndh gene of isoniazid resistant and susceptible Mycobacterium tuberculosis isolates from Brazil. (PMID 17294000) Jagielski T, et al. 2014. J. Antimicrob. Chemother. 69(9):2369-75 Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates. (PMID 24855126) Vilchèze C, et al. 2014. Microbiol Spectr 2(4):MGM2-0014-2013 Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities. (PMID 26104204) Rueda J, et al. 2015. Antimicrob. Agents Chemother. 59(12):7805-10 Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates. (PMID 26369965) Jagielski T, et al. 2015. J. Antimicrob. Chemother. 70(12):3214-21 Mutation profiling for detection of isoniazid resistance in Mycobacterium tuberculosis clinical isolates. (PMID 26311839) Islam MM, et al. 2019. Clin. Microbiol. Infect. 25(8):1041.e1-1041.e7 Detection of novel mutations associated with independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates. (PMID 30583053) Ezewudo M, et al. 2018. Sci Rep 8(1):15382 Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase. (PMID 30337678) |
Prevalence of Mycobacterium tuberculosis ndh with mutation conferring resistance to isoniazid 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 |
|---|---|---|---|---|---|
| Mycobacterium tuberculosis | 6.35% | 0% | 3.45% | 0% | 0% |
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): 800
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 |
|---|---|---|---|---|---|
| R13C | single resistance variant | PMID:17294000 | no data | no data | no data |
| V18A | single resistance variant | PMID:26311839 | no data | no data | no data |
| L50V | single resistance variant | PMID:26311839 | no data | no data | no data |
| T110A | single resistance variant | PMID:26104204 | no data | no data | no data |
| R268H | single resistance variant | PMID:26104204 | ReSeqTB-Minimal | no data | no data |
| A300P | single resistance variant | PMID:26311839 | no data | no data | no data |
| G313R | single resistance variant | PMID:26369965 | ReSeqTB-Indeterminate | no data | no data |
| G339A | single resistance variant | PMID:30583053 | no data | no data | no data |
| +nt969:g | insertion mutation from nucleotide sequence | PMID:30583053 | no data | no data | no data |
| Curator | Description | Most Recent Edit |
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