Escherichia coli UhpA with mutation conferring resistance to fosfomycin

Accession ARO:3003893
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 FamilyUhpT, UhpA
Drug Classfosfomycin
Resistance Mechanismantibiotic target alteration
Classification10 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Drug Class]
+ antibiotic resistant gene variant or mutant
+ UhpA [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)

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 for 82 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, 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 WGS
No prevalence data

Prevalence: protein knockout model

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGS
No prevalence data


Detection Models

Model Type: protein variant model

Model Definition: The protein variant model is an AMR detection model. Protein variant models are similar to protein homolog models - they detect the presence of a protein sequence based on its similarity to a curated reference sequence, but secondarily search submitted query sequences for curated sets of mutations shown clinically to confer resistance relative to wild-type. This model includes a protein reference sequence, a curated BLASTP cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of: single resistance variants, insertions, deletions, co-dependent resistance variants, nonsense SNPs, and/or frameshift mutations. Protein variant model matches to reference sequences are categorized on two criteria: strict and loose. A strict match has a BLASTP bitscore above the curated BLASTP cutoff value and contains at least one detected mutation from amongst the mapped resistance variants; a loose match has a BLASTP bitscore below the curated BLASTP cutoff value but still contains at least one detected mutation from amongst the mapped resistance variants. Regardless of BLASTP bitscore, if a sequence does not contain one of the mapped resistance variants, it is not considered a match and not detected by the protein variant model.

Legend:

  • discovered in clinical, agricultural, or environmental isolates
  • discovered via laboratory selection experiments


Bit-score Cut-off (blastP): 300


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



>gb|HG738867|+|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


Model Type: protein knockout model

Model Definition: An AMR detection model for instances where the absence of a protein - due to large-scale insertion elements, large deletions, or other methods of protein knockout - confers clinical resistance to a known antibiotic. These models include reference sequences. Protein knockout models are currently in development.


>gb|CDJ73205|+|Escherichia coli UhpA with mutation conferring resistance to fosfomycin [Escherichia coli str. K-12 substr. MC4100]
MITVALIDDHLIVRSGFAQLLGLEPDLQVVAEFGSGREALAGLPGRGVQVCICDISMPDISGLELLSQLPKGMATIMLSVHDSPALVEQA
LNAGARGFLSKRCSPDELIAAVHTVATGGCYLTPDIAIKLASGRQDPLTKRERQVAEKLAQGMAVKEIAAELGLSPKTVHVHRANLMEKL
GVSNDVELARRMFDGW


>gb|HG738867|+|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