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

Download Sequences
Accession ARO:3004157
Synonym(s)Rv2447c
CARD Short NameMtub_folC_PAS
DefinitionPoint mutations in the dihydrofolate synthetase folC gene shown clinically to confer resistance to p-aminosalicylic acid or other aminosalicylates. Mutations in folC inhibit bioactivation of PAS and thus confer resistance.
AMR Gene Familyaminosalicylate resistant dihydrofolate synthase
Drug Classsalicylic acid antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium aviumg, Mycobacterium intracellulareg+wgs, Mycobacterium lepraeg+wgs, Mycobacterium lepromatosisg+wgs, Mycobacterium marinumwgs, Mycobacterium tuberculosisg+wgs, Nocardia terpenicag+wgs, Rhodococcus rhodochrouswgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic para-aminosalicylic acid [Antibiotic]
+ aminosalicylate resistant dihydrofolate 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)
Resistomes

Prevalence of Mycobacterium tuberculosis folC 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 avium4.88%0%0%0%0%
Mycobacterium intracellulare2.44%0%2.04%0%0%
Mycobacterium leprae100%0%100%0%0%
Mycobacterium lepromatosis100%0%100%0%0%
Mycobacterium marinum0%0%3.77%0%0%
Mycobacterium tuberculosis2.87%0%3.26%0%0%
Nocardia terpenica100%0%100%0%0%
Rhodococcus rhodochrous0%0%11.11%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
T20Psingle resistance variantPMID:25421465no datano datano data
E40Gsingle resistance variantPMID:25421465no datano datano data
E40Qsingle resistance variantPMID:25421465no datano datano data
I43Tsingle resistance variantPMID:25421465no datano datano data
I43Ssingle resistance variantPMID:25421465no datano datano data
I43Asingle resistance variantPMID:25421465no datano datano data
R49Psingle resistance variantPMID:25421465no datano datano data
R49Wsingle resistance variantPMID:25421465no datano datano data
L56Vsingle resistance variantPMID:25421465no datano datano data
R91Wsingle resistance variantPMID:25421465no datano datano data
S150Csingle resistance variantPMID:25421465no datano datano data
S150Gsingle resistance variantPMID:25421465no datano datano data
E153Gsingle resistance variantPMID:25421465no datano datano data
E153Asingle resistance variantPMID:25421465no datano datano data
A420Vsingle resistance variantPMID:25421465no datano datano data

>gb|NP_216963.1|-|Mycobacterium tuberculosis folC with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
MNSTNSGPPDSGSATGVVPTPDEIASLLQVEHLLDQRWPETRIDPSLTRISALMDLLGSP
QRSYPSIHIAGTNGKTSVARMVDALVTALHRRTGRTTSPHLQSPVERISIDGKPISPAQY
VATYREIEPLVALIDQQSQASAGKGGPAMSKFEVLTAMAFAAFADAPVDVAVVEVGMGGR
WDATNVINAPVAVITPISIDHVDYLGADIAGIAGEKAGIITRAPDGSPDTVAVIGRQVPK
VMEVLLAESVRADASVAREDSEFAVLRRQIAVGGQVLQLQGLGGVYSDIYLPLHGEHQAH
NAVLALASVEAFFGAGAQRQLDGDAVRAGFAAVTSPGRLERMRSAPTVFIDAAHNPAGAS
ALAQTLAHEFDFRFLVGVLSVLGDKDVDGILAALEPVFDSVVVTHNGSPRALDVEALALA
AGERFGPDRVRTAENLRDAIDVATSLVDDAAADPDVAGDAFSRTGIVITGSVVTAGAART
LFGRDPQ


>gb|NC_000962.3|-|2746135-2747598|Mycobacterium tuberculosis folC with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
ATGAATTCGACGAATTCCGGCCCGCCTGACTCGGGATCGGCCACCGGCGTCGTGCCCACTCCGGACGAGATCGCGTCCCTGCTGCAGGTT
GAGCATCTACTCGACCAACGCTGGCCGGAGACCCGCATCGATCCGAGCCTGACCCGGATCAGCGCGTTGATGGACCTGCTGGGCTCGCCC
CAACGCAGCTATCCGTCGATCCATATCGCGGGCACCAACGGCAAGACCTCGGTGGCGCGCATGGTCGACGCGCTGGTCACCGCGCTGCAC
CGGCGCACCGGCCGAACCACCAGCCCACACCTGCAGTCACCGGTGGAACGCATTTCGATCGACGGCAAGCCGATCAGCCCGGCGCAGTAT
GTGGCGACCTACCGGGAGATCGAGCCGTTGGTGGCGCTGATCGACCAGCAGTCGCAGGCTTCTGCGGGTAAGGGTGGCCCGGCGATGAGC
AAGTTCGAGGTGCTCACCGCGATGGCGTTCGCGGCCTTTGCGGACGCGCCCGTCGACGTGGCAGTGGTCGAGGTGGGCATGGGCGGACGT
TGGGACGCCACCAACGTGATCAACGCACCGGTCGCCGTCATCACCCCGATCAGCATTGATCACGTCGACTATCTCGGTGCCGATATCGCC
GGGATCGCCGGGGAGAAGGCGGGCATCATCACTCGGGCCCCCGACGGTTCGCCGGACACCGTCGCGGTCATCGGGCGTCAGGTCCCGAAG
GTCATGGAGGTGCTGCTGGCCGAATCGGTGCGCGCCGACGCGTCGGTGGCCCGGGAGGATTCCGAATTCGCGGTGCTACGGCGACAGATC
GCGGTCGGCGGTCAGGTACTGCAACTGCAGGGCCTCGGCGGGGTTTACTCCGACATCTACTTGCCGCTGCACGGTGAACACCAGGCGCAC
AACGCGGTGCTCGCCCTCGCTTCCGTCGAGGCCTTTTTCGGTGCCGGTGCGCAGCGTCAGCTCGACGGCGACGCCGTCCGGGCCGGCTTT
GCCGCCGTCACCAGTCCCGGCCGGTTGGAGCGCATGCGCAGCGCACCCACGGTGTTCATCGACGCCGCGCACAATCCGGCCGGGGCGAGT
GCTCTGGCACAAACGCTGGCGCATGAGTTCGACTTCCGATTTCTGGTCGGGGTGCTCAGCGTGCTGGGCGACAAGGACGTGGACGGCATC
CTGGCCGCACTGGAGCCGGTGTTCGATTCCGTCGTCGTGACCCACAACGGGTCGCCGCGGGCGCTGGATGTCGAGGCCCTGGCGCTGGCG
GCCGGCGAGCGGTTCGGACCCGACCGGGTGCGCACCGCCGAGAACCTGCGCGATGCTATCGACGTTGCCACCTCACTGGTCGACGACGCC
GCCGCCGACCCGGATGTGGCCGGGGACGCATTCTCGAGAACCGGGATCGTCATCACCGGCTCGGTTGTCACCGCAGGGGCGGCTCGGACC
TTGTTCGGTCGTGATCCGCAATGA

Curator Acknowledgements
Curator Description Most Recent Edit