Escherichia coli uhpA with mutation conferring resistance to fosfomycin

Ontology CARD's Antibiotic Resistance Ontology
Accession ARO:3003893
CARD Short NameEcol_uhpA_FOF
DefinitionuhpA is a positive activator of the fosfomycin importer uhpT, thus mutations to uhpA confer fosfomycin resistance by reducing uhpT expression. Both knockout and amino acid substitution mutations have been found that confer resistance, with the Protein Knockout model describing the large, knockout mutations causing loss of function of the gene, and the Protein Variant model describing the amino acid substitutions.
AMR Gene Familyantibiotic-resistant UhpT
Drug Classphosphonic acid antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsEscherichia albertiig
Classification9 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Antibiotic]
+ antibiotic resistant gene variant or mutant
+ UhpA
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)

Resistomes

Prevalence of Escherichia coli uhpA 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Escherichia albertii1.43%0%0%0%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

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
G97Dsingle resistance variantPMID:20071153

>gb|CDJ73205.1|+|Escherichia coli uhpA with mutation conferring resistance to fosfomycin [Escherichia coli str. K-12 substr. MC4100]
MITVALIDDHLIVRSGFAQLLGLEPDLQVVAEFGSGREALAGLPGRGVQVCICDISMPDI
SGLELLSQLPKGMATIMLSVHDSPALVEQALNAGARGFLSKRCSPDELIAAVHTVATGGC
YLTPDIAIKLASGRQDPLTKRERQVAEKLAQGMAVKEIAAELGLSPKTVHVHRANLMEKL
GVSNDVELARRMFDGW



>gb|HG738867.1|+|2930708-2931298|Escherichia coli uhpA with mutation conferring resistance to fosfomycin [Escherichia coli str. K-12 substr. MC4100]
ATGATCACCGTTGCCCTTATAGACGATCACCTCATCGTCCGCTCCGGCTTTGCGCAGCTGCTGGGGCTGGAACCTGATTTGCAGGTAGTT
GCCGAGTTTGGTTCGGGGCGCGAGGCGCTGGCGGGGCTGCCGGGGCGCGGTGTGCAGGTGTGTATTTGCGATATCTCCATGCCCGATATC
TCCGGTCTGGAGCTGCTAAGCCAGCTGCCGAAAGGTATGGCGACGATTATGCTCTCCGTTCACGACAGTCCTGCGCTGGTTGAGCAGGCG
CTTAACGCGGGGGCACGCGGCTTTCTTTCCAAACGCTGTAGCCCGGATGAACTCATTGCTGCGGTGCATACGGTTGCCACGGGCGGCTGT
TATCTGACGCCGGATATTGCCATTAAACTGGCATCCGGTCGTCAGGACCCGCTAACCAAACGTGAACGCCAGGTGGCGGAAAAACTGGCG
CAAGGAATGGCGGTGAAAGAGATTGCCGCCGAACTGGGCTTGTCACCGAAAACGGTACACGTCCATCGCGCCAATCTGATGGAAAAACTG
GGCGTCAGTAACGACGTAGAGCTGGCGCGCCGCATGTTTGATGGCTGGTGA

Private model - RGI is not currently using this model.

Curator Acknowledgements
Curator Description Most Recent Edit