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

Accession ARO:3004184
CARD Short NameMtub_ribD_PAS
DefinitionribD is a Mycobacterium tuberculosis riboflavin biosynthesis enzyme. Point mutations in ribD cause enzyme overexpression, which allows the C-terminal reductase domain to act as an alternative dihydrofolate reductase. Thus, mutations in ribD confer resistance to DHFR inhibitors such as para-aminosalicylic acid.
AMR Gene Familyaminosalicylate resistant dihydrofolate reductase
Drug Classsalicylic acid antibiotic
Resistance Mechanismantibiotic target replacement
Resistomes with Sequence VariantsMycobacterium marinumg+wgs, Mycobacterium ulceransg+wgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ aminosalicylate resistant dihydrofolate reductase [AMR Gene Family]
+ confers_resistance_to_antibiotic para-aminosalicylic acid [Antibiotic]
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 ribD with mutation conferring resistance to para-aminosalicylic acid 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 (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Mycobacterium marinum100%0%86.79%0%
Mycobacterium ulcerans100%0%100%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): 300

Type of Antibiotic Resistance: Intrinsic or chromosomally-encoded

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 25421465G8R ntG-11A

>gb|CCP45469.1|+|Mycobacterium tuberculosis ribD with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
MPDSGQLGAADTPLRLLSSVHYLTDGELPQLYDYPDDGTWLRANFISSLDGGATVDGTSG
AMAGPGDRFVFNLLRELADVIVVGVGTVRIEGYSGVRMGVVQRQHRQARGQSEVPQLAIV
TRSGRLDRDMAVFTRTEMAPLVLTTTAVADDTRQRLAGLAEVIACSGDDPGTVDEAVLVS
QLAARGLRRILTEGGPTLLGTFVERDVLDELCLTIAPYVVGGLARRIVTGPGQVLTRMRC
AHVLTDDSGYLYTRYVKT



>gb|AL123456.3|+|2986839-2987615|Mycobacterium tuberculosis ribD with mutation conferring resistance to para-aminosalicylic acid [Mycobacterium tuberculosis H37Rv]
ATGCCCGACTCTGGTCAGCTCGGAGCCGCTGACACCCCGCTAAGGCTGCTCAGCTCGGTGCATTACCTCACCGACGGCGAACTCCCCCAG
CTTTACGACTATCCGGATGACGGCACCTGGTTGCGGGCGAACTTCATCAGCAGCTTGGACGGCGGCGCTACCGTCGATGGCACCAGCGGG
GCGATGGCCGGGCCCGGCGACCGATTCGTCTTCAACCTGTTGCGTGAACTTGCCGACGTCATCGTGGTCGGCGTGGGCACCGTGCGCATT
GAGGGCTACTCCGGCGTCCGGATGGGTGTCGTCCAGCGCCAGCACCGGCAGGCCCGAGGCCAAAGCGAAGTTCCGCAACTGGCAATCGTC
ACCAGGTCCGGTCGCCTTGACCGTGACATGGCGGTATTCACCCGGACCGAGATGGCACCGTTGGTGCTCACCACCACGGCGGTCGCCGAT
GACACGCGCCAGCGGCTCGCGGGCCTCGCCGAGGTGATCGCGTGCTCCGGCGACGATCCGGGCACGGTCGATGAGGCAGTGCTCGTGTCC
CAGCTCGCGGCTCGCGGTCTGCGCCGGATCCTTACCGAAGGCGGGCCGACGTTGCTCGGGACATTCGTCGAGCGTGACGTGCTCGACGAG
CTGTGTCTGACGATCGCCCCCTACGTCGTCGGCGGCCTGGCGCGCCGCATAGTGACGGGACCCGGGCAGGTGCTGACCCGGATGCGCTGT
GCCCATGTCCTCACCGACGACTCCGGCTACCTGTACACCCGCTACGTCAAGACCTGA