| Accession | ARO:3004876 |
| Synonym(s) | Rv1484 |
| CARD Short Name | Mtub_inhA_ETO |
| Definition | inhA is a enoyl-acyl carrier reductase used in lipid metabolism and farry acid biosynthesis. It is inhibited by ethionamide. Mutations in the promoter region or multiple copies of the inhA show marked resistance to ethionamide mediated inhibition of mycolic acid biosynthesis. |
| AMR Gene Family | inhA with mutations with conferring resistance to ethionamide |
| Drug Class | thioamide antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Classification | 9 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 + antibiotic resistant gene variant or mutant + thioamide antibiotic [Drug Class] + antibiotic resistant inhA |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic ethionamide [Antibiotic] + inhA with mutations with conferring resistance to ethionamide [AMR Gene Family] |
| Publications | Manjunatha UH, et al. 2015. Sci Transl Med 7(269):269ra3 Direct inhibitors of InhA are active against Mycobacterium tuberculosis. (PMID 25568071) Rawat R, et al. 2003. Proc. Natl. Acad. Sci. U.S.A. 100(24):13881-6 The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: adduct affinity and drug resistance. (PMID 14623976) Ho YM, et al. 2009. Antimicrob. Agents Chemother. 53(9):4010-2 Contribution of dfrA and inhA mutations to the detection of isoniazid-resistant Mycobacterium tuberculosis isolates. (PMID 19581462) 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) 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 inhA mutations conferring resistance to ethionamide 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): 500
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 |
|---|---|---|---|---|---|
| I21T | single resistance variant | no data | ReSeqTB-High | no data | WHO-U |
| I21V | single resistance variant | no data | ReSeqTB-High | no data | WHO-U |
| S94A | single resistance variant | no data | no data | no data | WHO-R |
| I194T | single resistance variant | no data | ReSeqTB-Moderate | no data | no data |
| Curator | Description | Most Recent Edit |
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