Mycobacterium tuberculosis intrinsic murA conferring resistance to fosfomycin

Accession ARO:3003784
Synonym(s)Rv1315
CARD Short NameMtub_murA_FOF
DefinitionMycobacterium tuberculosis murA confers intrinsic resistance to fosfomycin. The presence of an aspartic acid residue in place of the critical cysteine at position 117 that enables fosfomycin binding is believed to be responsible for this intrinsic resistance.
AMR Gene Familyantibiotic-resistant murA transferase
Drug Classphosphonic acid antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsMycobacterium aviumg+wgs, Mycobacterium colombienseg+wgs, Mycobacterium intracellulareg+wgs, Mycobacterium kansasiig+wgs, Mycobacterium lepraeg+wgs, Mycobacterium lepromatosisg+wgs, Mycobacterium marinumg+wgs, Mycobacterium tuberculosisg+wgs, Mycobacterium ulceransg+wgs, Mycolicibacterium fortuitumg+wgs, Mycolicibacterium septicumwgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Antibiotic]
+ antibiotic-resistant murA transferase [AMR Gene Family]
Publications

De Smet KA, et al. 1999. Microbiology (Reading, Engl.) 145 ( Pt 11):3177-84 Alteration of a single amino acid residue reverses fosfomycin resistance of recombinant MurA from Mycobacterium tuberculosis. (PMID 10589726)

Isaza JP, et al. 2012. FEMS Microbiol. Lett. 330(2):113-20 Whole genome shotgun sequencing of one Colombian clinical isolate of Mycobacterium tuberculosis reveals DosR regulon gene deletions. (PMID 22404577)

Resistomes

Prevalence of Mycobacterium tuberculosis intrinsic murA conferring resistance to fosfomycin 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 avium100%0%89.95%0%
Mycobacterium colombiense100%0%100%0%
Mycobacterium intracellulare100%0%73.47%0%
Mycobacterium kansasii100%0%100%0%
Mycobacterium leprae100%0%100%0%
Mycobacterium lepromatosis100%0%100%0%
Mycobacterium marinum100%0%86.79%0%
Mycobacterium tuberculosis99.8%0%72.62%0%
Mycobacterium ulcerans100%0%100%0%
Mycolicibacterium fortuitum50%0%75.86%0%
Mycolicibacterium septicum0%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): 750

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:


>gb|NP_215831.1|+|Mycobacterium tuberculosis intrinsic murA conferring resistance to fosfomycin [Mycobacterium tuberculosis H37Rv]
MAERFVVTGGNRLSGEVAVGGAKNSVLKLMAATLLAEGTSTITNCPDILDVPLMAEVLRG
LGATVELDGDVARITAPDEPKYDADFAAVRQFRASVCVLGPLVGRCKRARVALPGGDAIG
SRPLDMHQAGLRQLGAHCNIEHGCVVARAETLRGAEIQLEFPSVGATENILMAAVVAEGV
TTIHNAAREPDVVDLCTMLNQMGAQVEGAGSPTMTITGVPRLHPTEHRVIGDRIVAATWG
IAAAMTRGDISVAGVDPAHLQLVLHKLHDAGATVTQTDASFRVTQYERPKAVNVATLPFP
GFPTDLQPMAIALASIADGTSMITENVFEARFRFVEEMIRLGADARTDGHHAVVRGLPQL
SSAPVWCSDIRAGAGLVLAGLVADGDTEVHDVFHIDRGYPLFVENLVSLGAEIERVCC



>gb|NC_000962.3|+|1470321-1471577|Mycobacterium tuberculosis intrinsic murA conferring resistance to fosfomycin [Mycobacterium tuberculosis H37Rv]
GTGGCCGAGCGTTTCGTCGTGACTGGGGGCAACCGGTTATCAGGCGAAGTGGCCGTCGGCGGCGCCAAGAACAGCGTGCTCAAGCTCATG
GCTGCGACGTTGTTGGCCGAGGGCACCAGCACGATCACCAACTGTCCCGACATCCTCGATGTGCCGCTGATGGCGGAGGTACTGCGTGGT
CTGGGCGCCACCGTCGAACTCGACGGTGACGTGGCCCGGATCACCGCACCTGACGAGCCGAAGTACGATGCCGACTTCGCTGCGGTGCGG
CAATTCCGCGCCTCGGTCTGTGTGCTGGGACCGCTGGTCGGGCGGTGCAAACGGGCCAGGGTCGCGCTGCCGGGCGGTGACGCGATCGGG
TCGCGTCCGTTGGATATGCACCAGGCGGGCCTACGGCAATTGGGTGCCCACTGCAACATCGAGCACGGCTGCGTGGTAGCCCGAGCGGAA
ACGTTGCGCGGTGCGGAGATTCAGTTGGAGTTCCCCTCGGTGGGAGCCACCGAGAACATCTTGATGGCCGCCGTGGTGGCCGAGGGAGTC
ACCACTATTCACAATGCGGCTCGAGAACCCGACGTCGTCGACTTGTGCACGATGTTGAACCAGATGGGCGCACAGGTCGAAGGTGCGGGT
TCGCCGACAATGACCATCACCGGTGTCCCGCGGCTGCATCCAACCGAGCACCGGGTGATCGGAGACCGTATCGTTGCCGCCACATGGGGC
ATCGCTGCCGCAATGACCCGTGGTGATATATCAGTGGCGGGCGTAGACCCGGCGCATCTGCAGCTGGTGCTGCACAAATTGCACGACGCG
GGCGCAACCGTCACCCAGACTGACGCCAGCTTCCGGGTGACCCAGTACGAGCGTCCGAAGGCTGTCAACGTTGCGACCTTGCCGTTCCCC
GGGTTTCCCACGGATCTGCAGCCGATGGCTATCGCTTTGGCGTCGATCGCCGACGGCACATCGATGATCACGGAGAACGTGTTCGAGGCG
CGGTTCCGCTTCGTTGAAGAGATGATCCGGCTCGGTGCAGACGCTCGGACCGACGGGCACCACGCCGTGGTGCGGGGCCTCCCGCAGCTG
TCGAGCGCTCCGGTGTGGTGTTCGGACATCCGTGCCGGGGCCGGCTTGGTGCTGGCGGGGCTCGTTGCCGACGGCGACACCGAGGTCCAC
GATGTATTCCACATCGATCGCGGATATCCGTTGTTCGTGGAGAACCTGGTGAGTCTCGGTGCCGAGATCGAACGGGTATGCTGTTAG