| Accession | ARO:3004721 |
| Synonym(s) | Rv1630 |
| CARD Short Name | Mtub_rpsA_PZA |
| Definition | RpsA, the 30S ribosomal protein S1 of Mycobacterium tuberculosis, is involved in trans-translation and is targeted by pyrazinonic acid, the active form of the antibiotic pyrazinamide, which disrupts the initiation of mRNA translation. Mutations in the amino acid sequence of rpsA can confer resistance to pyrazinamide maintaining rpsA function. |
| AMR Gene Family | pyrazinamide resistant rpsA |
| Drug Class | pyrazine antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| 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 + pyrazine antibiotic [Drug Class] + antibiotic resistant gene variant or mutant |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic pyrazinamide [Antibiotic] + pyrazinamide resistant rpsA [AMR Gene Family] |
| Publications | Khan MT, et al. 2019. Sci Rep 9(1):7482 Structural and free energy landscape of novel mutations in ribosomal protein S1 (rpsA) associated with pyrazinamide resistance. (PMID 31097767) Khan MT, et al. . J. Biol. Regul. Homeost. Agents 32(3):705-709 Pyrazinamide-resistant mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa and rpsA mutations. (PMID 29921403) Khan MT, et al. 2018. Comput Struct Biotechnol J 16:379-387 Insight into novel clinical mutants of RpsA-S324F, E325K, and G341R of Mycobacterium tuberculosis associated with pyrazinamide resistance. (PMID 30402208) Shi W, et al. 2019. Antimicrob. Agents Chemother. 63(6): Introducing RpsA Point Mutations Δ438A and D123A into the Chromosome of Mycobacterium tuberculosis Confirms Their Role in Causing Resistance to Pyrazinamide. (PMID 30858213) 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 rpsA mutations conferring resistance to pyrazinamide 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): 930
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 |
|---|---|---|---|---|---|
| D123A | single resistance variant | PMID:30858213 | no data | no data | no data |
| S324F | single resistance variant | PMID:30402208 | no data | no data | no data |
| E325K | single resistance variant | PMID:30402208 | no data | no data | no data |
| G341R | single resistance variant | PMID:30402208 | no data | no data | no data |
| D342N | single resistance variant | PMID:31097767 | no data | no data | no data |
| D343N | single resistance variant | PMID:31097767 | no data | no data | no data |
| A344P | single resistance variant | PMID:31097767 | no data | no data | no data |
| I351F | single resistance variant | PMID:31097767 | no data | no data | no data |
| A381V | single resistance variant | no data | ReSeqTB-High | no data | no data |
| A412V | single resistance variant | no data | ReSeqTB-High | no data | no data |
| -A438 | deletion mutation from peptide sequence | PMID:30858213 | no data | no data | no data |
| A440T | single resistance variant | no data | ReSeqTB-High | no data | no data |
| Ter482fs | frameshift mutation | no data | ReSeqTB-High | no data | no data |
| Curator | Description | Most Recent Edit |
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