| Accession | ARO:3003775 |
| CARD Short Name | Ecol_murA_FOF |
| Definition | murA or UDP-N-acetylglucosamine enolpyruvyl transferase catalyses the initial step in peptidoglycan biosynthesis and is inhibited by fosfomycin. Overexpression of murA through mutations such as Asp369Asn and Leu370Ile confers fosfomycin resistance. Extensive evidence has shown the significance of C115 mutations in conferring fosfomycin resistance since this residue represents a primary binding site for the antibiotic across many species. |
| AMR Gene Family | antibiotic-resistant murA transferase |
| Drug Class | phosphonic acid antibiotic |
| Resistance Mechanism | antibiotic target alteration |
| Classification | 8 ontology terms | Show + process or component of antibiotic biology or chemistry + mechanism of antibiotic resistance + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + antibiotic molecule + phosphonic acid antibiotic [Drug Class] + antibiotic resistant gene variant or mutant |
| Parent Term(s) | 2 ontology terms | Show + confers_resistance_to_antibiotic fosfomycin [Antibiotic] + antibiotic-resistant murA transferase [AMR Gene Family] |
| Publications | Takahata S, et al. 2010. Int J Antimicrob Agents 35(4): 333-337. Molecular mechanisms of fosfomycin resistance in clinical isolates of Escherichia coli. (PMID 20071153) Cheng G, et al. 2013. Biotechnol. Lett. 35(2):273-8 Identification of a novel fosfomycin-resistant UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) from a soil metagenome. (PMID 23143172) Kim DH, et al. 1996. Biochemistry 35(15):4923-8 Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. (PMID 8664284) Wanke C, et al. 1993. Eur. J. Biochem. 218(3):861-70 Evidence that the reaction of the UDP-N-acetylglucosamine 1-carboxyvinyltransferase proceeds through the O-phosphothioketal of pyruvic acid bound to Cys115 of the enzyme. (PMID 8281938) |
Prevalence of Escherichia coli murA with mutation conferring resistance to fosfomycin 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).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| No prevalence data | |||||
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): 800
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).| Mutation | Mutation type | PubMed |
|---|---|---|
| C115S | single resistance variant | PMID:8281938 |
| C115D | single resistance variant | PMID:8664284 |
| C115E | single resistance variant | PMID:8664284 |
| D369N | single resistance variant | PMID:20071153 |
| L370I | single resistance variant | PMID:20071153 |
| Curator | Description | Most Recent Edit |
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