Mycobacterium leprae folP with mutation conferring resistance to dapsone

Accession ARO:3003389
CARD Short NameMlep_folP_DAO
DefinitionDapsone inhibits bacterial synthesis of dihydrofolic acid by competing with with para-aminobenzoate for the active site of dihydropteroate synthetase. Point mutation within the Mycobacterium leprae folP gene results in lowered affinity of dapsone for folP.
AMR Gene Familydapsone resistant dihydropteroate synthase folP
Drug Classsulfone antibiotic
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ dapsone resistant dihydropteroate synthase folP [AMR Gene Family]
+ confers_resistance_to_antibiotic dapsone [Antibiotic]
Publications

Nakata N, et al. 2011. Antimicrob Agents Chemother 55(2): 762-766. Mutation analysis of the Mycobacterium leprae folP1 gene and dapsone resistance. (PMID 21115799)

You EY, et al. 2004. J Infect 50(1): 6-11. Mutations in genes related to drug resistance in Mycobacterium leprae isolates from leprosy patients in Korea. (PMID 15603834)

Maeda S, et al. 2001. Antimicrob. Agents Chemother. 45(12):3635-9 Multidrug resistant Mycobacterium leprae from patients with leprosy. (PMID 11709358)

Resistomes

Prevalence of Mycobacterium leprae folP with mutation conferring resistance to dapsone 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
No prevalence data


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

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 typePubMed
V48Fsingle resistance variantPMID:21115799
V48Gsingle resistance variantPMID:21115799
V48Asingle resistance variantPMID:21115799
T53Nsingle resistance variantPMID:21115799
T53Psingle resistance variantPMID:21115799
T53Isingle resistance variantPMID:21115799
T53Asingle resistance variantPMID:21115799
R54Gsingle resistance variantPMID:21115799
P55Lsingle resistance variantPMID:21115799
P55Ssingle resistance variantPMID:15603834
P55Hsingle resistance variantPMID:21115799
P55Tsingle resistance variantPMID:21115799
P55Rsingle resistance variantPMID:15603834
P55Asingle resistance variantPMID:21115799

>gb|CAC29732.1|+|Mycobacterium leprae folP with mutation conferring resistance to dapsone [Mycobacterium leprae TN]
MSLAPVQVIGVLNVTDNSFSDGGRYLDPDDAVQHGLAMVAEGAAIVDVGGESTRPGAIRT
DPRVELSRIVPVVKELAAQGITVSIDTTRADVARAALQSGARIVNDVSGGRADPAMAPLV
AEAGVAWVLMHWRLMSAERPYEAPNYRDVVAEVRADLLAGVDQAVAAGVDPGSLVIDPGL
GFAKTGQHNWALLNALPELVATGVPILLGASRKRFLGRLLAGADGAVRPPDGRETATAVI
SALAALHGAWGVRVHDVRASVDALKVVGAWLHAGPQIEKVRCDG



>gb|AL450380.1|+|296696-297550|Mycobacterium leprae folP with mutation conferring resistance to dapsone [Mycobacterium leprae TN]
GTGAGTTTGGCGCCAGTGCAGGTTATTGGGGTTTTGAACGTCACTGACAATTCGTTCTCAGATGGCGGACGTTACCTTGATCCTGACGAT
GCTGTCCAGCACGGCCTGGCAATGGTCGCGGAAGGCGCGGCGATTGTCGACGTCGGTGGCGAATCGACCCGGCCCGGTGCCATTAGGACC
GATCCTCGAGTTGAACTCTCTCGTATCGTTCCTGTCGTAAAAGAACTTGCAGCACAGGGGATTACAGTAAGTATCGATACTACGCGCGCT
GATGTTGCACGGGCGGCGCTGCAAAGCGGCGCACGGATCGTCAACGATGTGTCTGGTGGGCGAGCAGATCCCGCGATGGCTCCTCTGGTG
GCTGAAGCCGGTGTTGCGTGGGTGTTGATGCACTGGCGACTGATGTCGGCTGAACGGCCGTATGAGGCTCCGAATTACCGCGACGTGGTG
GCTGAAGTGCGTGCCGACCTACTGGCTGGTGTCGATCAGGCTGTGGCCGCAGGTGTTGATCCTGGGAGTCTAGTGATCGATCCCGGGCTT
GGATTCGCCAAGACGGGACAGCACAATTGGGCGCTGCTGAATGCGTTACCGGAGTTGGTGGCTACTGGGGTCCCGATTCTACTTGGCGCC
TCGCGTAAACGGTTCCTGGGTAGGTTATTAGCTGGGGCTGATGGCGCGGTACGACCGCCGGACGGACGTGAGACGGCGACCGCGGTGATT
TCCGCACTTGCTGCCCTACACGGGGCTTGGGGTGTTCGGGTGCACGATGTGCGTGCCTCGGTCGACGCACTCAAGGTCGTCGGGGCTTGG
CTGCATGCTGGGCCGCAGATTGAAAAGGTTAGATGTGATGGCTGA

Curator Acknowledgements
Curator Description Most Recent Edit