Mycobacterium tuberculosis thyA with mutation conferring resistance to para-aminosalicylic acid

Download Sequences
Accession ARO:3004153
Synonym(s)Rv2764c
CARD Short NameMtub_thyA_PAS
DefinitionPoint mutations in the thymidylate synthetase thyA gene shown clinically to confer resistance to para-aminosalicylic acid. Loss-of-function mutations in thyA disrupt the catalytic activity and substrate-binding affinity, thus conferring resistance.
AMR Gene Familyaminosalicylate resistant thymidylate synthase
Drug Classsalicylic acid antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium tuberculosisg+wgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic para-aminosalicylic acid [Antibiotic]
+ aminosalicylate resistant thymidylate synthase [AMR Gene Family]
Publications

Zhang X, et al. 2015. Antimicrob. Agents Chemother. 59(2):1320-4 Genetic determinants involved in p-aminosalicylic acid resistance in clinical isolates from tuberculosis patients in northern China from 2006 to 2012. (PMID 25421465)

The CRyPTIC Consortium 2022. PLoS Biol 20(8):e3001721 A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics. (PMID 35944069)
Resistomes

Prevalence of Mycobacterium tuberculosis thyA with mutation conferring resistance to para-aminosalicylic acid 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Mycobacterium tuberculosis14.96%0%27.25%0%0%
Show Perfect Only


Detection Models

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

Type of Antibiotic Resistance: Intrinsic or chromosomally-encoded

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).

MutationMutation typePubMedReSeqTBCRyPTICWHO
T22Asingle resistance variantPMID:25421465no datano datano data
Y36Csingle resistance variantPMID:25421465no datano datano data
H75Nsingle resistance variantPMID:25421465no datano datano data
G76Ternonsense mutationPMID:25421465no datano datano data
V77Fsingle resistance variantPMID:25421465no datano datano data
W83Ternonsense mutationPMID:25421465no datano datano data
W83Csingle resistance variantPMID:25421465no datano datano data
G91Rsingle resistance variantPMID:25421465no datano datano data
W98Ternonsense mutationPMID:25421465no datano datano data
W101Rsingle resistance variantPMID:25421465no datano datano data
S105Psingle resistance variantPMID:25421465no datano datano data
-nt111:tdeletion mutation from nucleotide sequencePMID:25421465no datano datano data
R126Qsingle resistance variantPMID:25421465no datano datano data
F152Vsingle resistance variantPMID:25421465no datano datano data
C161Tsingle resistance variantPMID:25421465no datano datano data
T202Asingle resistance variantPMID:25421465no datano datano data
H207Rsingle resistance variantPMID:25421465no datano datano data
I211Vsingle resistance variantPMID:25421465no datano datano data
+nt217:cacgagcacinsertion mutation from nucleotide sequencePMID:25421465no datano datano data
P224Lsingle resistance variantPMID:25421465no datano datano data
R235Psingle resistance variantPMID:25421465no datano datano data
-nt260:cdeletion mutation from nucleotide sequencePMID:25421465no datano datano data
+nt372:tinsertion mutation from nucleotide sequencePMID:25421465no datano datano data
-nt472:cdeletion mutation from nucleotide sequencePMID:25421465no datano datano data

>gb|NP_217280.1|-|Mycobacterium tuberculosis thyA with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
MTPYEDLLRFVLETGTPKSDRTGTGTRSLFGQQMRYDLSAGFPLLTTKKVHFKSVAYELL
WFLRGDSNIGWLHEHGVTIWDEWASDTGELGPIYGVQWRSWPAPSGEHIDQISAALDLLR
TDPDSRRIIVSAWNVGEIERMALPPCHAFFQFYVADGRLSCQLYQRSADLFLGVPFNIAS
YALLTHMMAAQAGLSVGEFIWTGGDCHIYDNHVEQVRLQLSREPRPYPKLLLADRDSIFE
YTYEDIVVKNYDPHPAIKAPVAV


>gb|NC_000962.3|-|3073680-3074471|Mycobacterium tuberculosis thyA with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
GTGACGCCATACGAGGACCTGCTGCGCTTCGTGCTCGAAACGGGTACGCCCAAATCCGACCGCACCGGCACCGGAACCCGCAGCCTGTTC
GGCCAGCAGATGCGCTATGATTTGTCGGCCGGTTTCCCGCTGCTCACTACCAAGAAAGTCCATTTCAAATCGGTAGCCTACGAGCTGCTG
TGGTTTTTGCGCGGCGATTCCAATATCGGTTGGCTGCACGAGCACGGAGTCACCATCTGGGACGAATGGGCAAGTGATACAGGCGAACTC
GGGCCGATCTACGGTGTACAATGGCGATCGTGGCCGGCTCCATCCGGTGAGCACATCGACCAGATCAGCGCGGCGCTGGATTTGCTGCGC
ACCGATCCCGATTCCCGGCGCATCATCGTGTCGGCCTGGAACGTCGGCGAAATCGAGCGGATGGCGCTGCCGCCCTGTCATGCGTTCTTC
CAGTTCTACGTCGCCGATGGCCGGCTGAGCTGTCAGCTCTACCAACGCAGCGCCGACCTGTTTCTGGGTGTGCCGTTCAACATCGCCAGC
TATGCGTTGCTCACCCACATGATGGCCGCCCAGGCCGGCTTGTCGGTCGGCGAGTTCATCTGGACCGGTGGCGACTGCCACATCTACGAC
AATCACGTCGAGCAAGTACGGCTGCAGCTCAGCCGCGAGCCGCGGCCATATCCGAAACTACTTCTAGCCGACCGGGATTCAATCTTCGAG
TACACCTATGAAGACATCGTTGTGAAGAACTACGATCCGCATCCGGCGATCAAAGCTCCAGTCGCGGTATGA

Curator Acknowledgements
Curator Description Most Recent Edit