| Accession | ARO:3003393 |
| Synonym(s) | Rv1484 |
| CARD Short Name | Mtub_inhA_INH |
| Definition | inhA is a enoyl-acyl carrier reductase used in lipid metabolism and farry acid biosynthesis. It is inhibited by isoniazid. mutations in the promoter region or multiple copies of the inhA shows marked resistance to isoniazid mediated inhibition of mycolic acid biosynthesis. |
| AMR Gene Family | isoniazid resistant inhA |
| Drug Class | isoniazid-like antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium tuberculosisg+wgs |
| 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 + isoniazid-like antibiotic [Drug Class] + antibiotic resistant inhA |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic isoniazid [Antibiotic] + isoniazid resistant inhA [AMR Gene Family] |
| Publications | Campbell PJ, et al. 2011. Antimicrob Agents Chemother 55(5): 2032-2041. Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis. (PMID 21300839) Khadka JB, et al. 2011. Nepal Med Coll J 13(3): 147-151. Study of rifampicin and isoniazid resistance mutation genes of M. tuberculosis isolates in Nepal. (PMID 22808802) Banerjee A, et al. 1994. Science 263(5144): 227-230. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. (PMID 8284673) Basso LA, et al. 1998. J Infect Dis 178(3): 769-775. Mechanisms of isoniazid resistance in Mycobacterium tuberculosis: enzymatic characterization of enoyl reductase mutants identified in isoniazid-resistant clinical isolates. (PMID 9728546) Morlock GP, et al. 2003. Antimicrob Agents Chemother 47(12): 3799-3805. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. (PMID 14638486) Ristow M, et al. 1995. Lancet 346(8973): 502-503. New isoniazid/ethionamide resistance gene mutation and screening for multidrug-resistant Mycobacterium tuberculosis strains. (PMID 7637495) Leung ET, et al. 2006. Antimicrob. Agents Chemother. 50(3):1075-8 Molecular characterization of isoniazid resistance in Mycobacterium tuberculosis: identification of a novel mutation in inhA. (PMID 16495272) Machado D, et al. 2013. J. Antimicrob. Chemother. 68(8):1728-32 High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations. (PMID 23539241) Hazbón MH, et al. 2006. Antimicrob. Agents Chemother. 50(8):2640-9 Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. (PMID 16870753) 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 inhA mutations conferring resistance to isoniazid 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI |
|---|---|---|---|---|
| Mycobacterium tuberculosis | 18.85% | 0% | 2.02% | 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): 500
Legend:
Published Variants:
| PMID: 9728546 | I16T I21V I21T I47T V78A S94A I95P |
| PMID: 16495272 | I194T |
| PMID: 23539241 | I194T |
| PMID: 30583053 | G3G G141E |
| PMID: 30337678 | S94A T162S I194T |
ReSeqTB:
| High Confidence | T162S I194T |
| Minimal Confidence | S94A |