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 413 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 GI
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

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 21115799V48F V48A V48G T53P T53N T53A T53I R54G P55T P55A P55H P55L
PMID: 15603834P55R P55S
PMID: 11709358T53A T53I P55L

>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