| Accession | ARO:3003463 |
| Synonym(s) | Rv2245 |
| CARD Short Name | Mtub_kasA_INH |
| Definition | Specific mutations on the Mycobacterium tuberculosis kasA gene resulting in lowered affinity of isoniazid, resulting in resistance. |
| AMR Gene Family | antibiotic resistant kasA |
| 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 kasA [AMR Gene Family] |
| Publications | Lee AS, et al. 1999. Antimicrob Agents Chemother 43(8): 2087-2089. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore. (PMID 10428945) Mdluli K, et al. 1998. Science 280(5369): 1607-1610. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid. (PMID 9616124) 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 kasA mutant 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 | 8.61% | 0% | 19.22% | 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): 750
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 |
|---|---|---|---|---|---|
| D66N | single resistance variant | PMID:9616124 | no data | no data | no data |
| R121K | single resistance variant | PMID:10428945 | no data | no data | no data |
| G269S | single resistance variant | PMID:10428945 | no data | no data | no data |
| G312S | single resistance variant | PMID:10428945 | ReSeqTB-None | no data | no data |
| G387D | single resistance variant | PMID:10428945 | no data | no data | no data |
| F413L | single resistance variant | PMID:9616124 | no data | no data | no data |
| Curator | Description | Most Recent Edit |
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