| Accession | ARO:3003458 |
| Synonym(s) | Rv3854c |
| CARD Short Name | Mtub_ethA_ETO |
| Definition | Mycobacterium tuberculosis ethA (Rv3854c) is a mono-oxygenase enzyme which activates the antibiotic ethionamide in vivo. Mutations in ethA confer resistance to ethionamide by modulating the activation and activity of the ethionamide prodrug. |
| AMR Gene Family | ethionamide resistant ethA |
| Drug Class | thioamide antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Mycobacterium marinumg+wgs, 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 + thioamide antibiotic [Drug Class] + antibiotic resistant ethA |
| Parent Term(s) | 2 ontology terms | Show + ethionamide resistant ethA [AMR Gene Family] + confers_resistance_to_antibiotic ethionamide [Antibiotic] |
| Publications | 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) DeBarber AE, et al. 2000. Proc. Natl. Acad. Sci. U.S.A. 97(17):9677-82 Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. (PMID 10944230) de Welzen L, et al. 2017. Antimicrob. Agents Chemother. 61(12): Whole-Transcriptome and -Genome Analysis of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates Identifies Downregulation ofas a Mechanism of Ethionamide Resistance. (PMID 28993337) 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 ethA with mutation conferring resistance to ethionamide 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 marinum | 85.71% | 0% | 77.36% | 0% |
| Mycobacterium tuberculosis | 0.82% | 0% | 0.8% | 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): 900
Legend:
Published Variants:
| PMID: 14638486 | G43S E223K I338S G385D T392A G413D R463S -nt110:A -nt1290:C +nt338:A -nt65:1 -nt703:T -nt768:G +nt811:1 |
| PMID: 10944230 | G43C P51L D58A Y84D T186K T342K A381P |
| PMID: 28993337 | ntT-11C |
| PMID: 30337678 | G11fs Y147STOP S266R H281P T342K N379D P422fs |
ReSeqTB:
| High Confidence | T342K N379D P422fs G11fs Y147STOP H281P |