Escherichia coli GlpT with mutation conferring resistance to fosfomycin

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Accession ARO:3003889
CARD Short NameEcol_GlpT_FOF
DefinitionPoint mutations to the active importer GlpT, which is involved with the uptake of many phosphorylated sugars, confer resistance to fosfomycin by reducing import of the drug into the bacteria.
AMR Gene Familyantibiotic-resistant GlpT
Drug Classphosphonic acid antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsCitrobacter amalonaticusg+wgs, Citrobacter freundiig+p+wgs, Citrobacter koserig+wgs, Citrobacter portucalensisg+wgs, Citrobacter werkmaniig+wgs, Citrobacter youngaeg+wgs, Cronobacter condimentig+wgs, Cronobacter dublinensisg+wgs, Cronobacter malonaticusg+wgs, Cronobacter sakazakiig+wgs, Cronobacter turicensiswgs, Cronobacter universalisg+wgs, Edwardsiella tardag+wgs, Enterobacter cloacaewgs, Enterobacter hormaecheiwgs, Enterobacter kobeiwgs, Escherichia albertiig+wgs, Escherichia colig+p+wgs, Escherichia fergusoniig+wgs, Escherichia marmotaeg+wgs, Salmonella bongorig+wgs, Salmonella entericag+wgs, Serratia marcescensg+wgs, Serratia rubidaeag+wgs, Shigella boydiig+wgs, Shigella dysenteriaeg+wgs, Shigella flexnerig+wgs, Shigella sonneig+wgs
Classification8 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Antibiotic]
+ antibiotic resistant gene variant or mutant
+ antibiotic-resistant GlpT [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)

Nilsson AI, et al. 2003. Antimicrob Agents Chemother 47(9): 2850-2858. Biological costs and mechanisms of fosfomycin resistance in Escherichia coli. (PMID 12936984)
Resistomes

Prevalence of Escherichia coli GlpT 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
Citrobacter amalonaticus72.73%0%78.18%0%0%
Citrobacter freundii90.16%0.31%86.46%0%0%
Citrobacter koseri100%0%98.2%0%0%
Citrobacter portucalensis74.07%0%95.5%0%0%
Citrobacter werkmanii100%0%100%0%0%
Citrobacter youngae66.67%0%100%0%0%
Cronobacter condimenti100%0%100%0%0%
Cronobacter dublinensis100%0%97.44%0%0%
Cronobacter malonaticus100%0%96.36%0%0%
Cronobacter sakazakii100%0%98.65%0%0%
Cronobacter turicensis0%0%91.67%0%0%
Cronobacter universalis100%0%100%0%0%
Edwardsiella tarda30%0%13.33%0%0%
Enterobacter cloacae0%0%0.32%0%0%
Enterobacter hormaechei0%0%0.04%0%0%
Enterobacter kobei0%0%0.44%0%0%
Escherichia albertii100%0%100%0%0%
Escherichia coli52.22%0.04%83.97%0%75.04%
Escherichia fergusonii100%0%100%0%0%
Escherichia marmotae100%0%97.92%0%0%
Salmonella bongori100%0%100%0%0%
Salmonella enterica94.83%0%98.55%0%0%
Serratia marcescens27.27%0%26.61%0%0%
Serratia rubidaea100%0%100%0%0%
Shigella boydii86.67%0%92.22%0%0%
Shigella dysenteriae100%0%96.67%0%0%
Shigella flexneri94%0%99.22%0%0%
Shigella sonnei100%0%95.62%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): 850

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
E448Ksingle resistance variantPMID:20071153
E448K,G33Rmultiple resistance variantsPMID:20071153
E448K,Q444E,E443Q,L297Fmultiple resistance variantsPMID:20071153
E448K,G302Dmultiple resistance variantsPMID:20071153
-nt602:20deletion mutation from nucleotide sequencePMID:20071153

>gb|CDJ72593.1|-|Escherichia coli GlpT with mutation conferring resistance to fosfomycin [Escherichia coli str. K-12 substr. MC4100]
MLSIFKPAPHKARLPAAEIDPTYRRLRWQIFLGIFFGYAAYYLVRKNFALAMPYLVEQGF
SRGDLGFALSGISIAYGFSKFIMGSVSDRSNPRVFLPAGLILAAAVMLFMGFVPWATSSI
AVMFVLLFLCGWFQGMGWPPCGRTMVHWWSQKERGGIVSVWNCAHNVGGGIPPLLFLLGM
AWFNDWHAALYMPAFCAILVALFAFAMMRDTPQSCGLPPIEEYKNDYPDDYNEKAEQELT
AKQIFMQYVLPNKLLWYIAIANVFVYLLRYGILDWSPTYLKEVKHFALDKSSWAYFLYEY
AGIPGTLLCGWMSDKVFRGNRGATGVFFMTLVTIATIVYWMNPAGNPTVDMICMIVIGFL
IYGPVMLIGLHALELAPKKAAGTAAGFTGLFGYLGGSVAASAIVGYTVDFFGWDGGFMVM
IGGSILAVILLIVVMIGEKRRHEQLLQERNGG


>gb|HG738867.1|-|2233289-2234647|Escherichia coli GlpT with mutation conferring resistance to fosfomycin [Escherichia coli str. K-12 substr. MC4100]
ATGTTGAGTATTTTTAAACCAGCGCCACACAAAGCGCGCTTACCTGCCGCGGAGATCGATCCGACTTATCGTCGATTGCGCTGGCAAATT
TTCCTGGGGATATTCTTTGGCTATGCGGCTTACTATTTGGTTCGTAAGAACTTTGCGCTTGCTATGCCTTATCTGGTTGAGCAGGGATTC
TCACGCGGTGATTTAGGTTTTGCCCTTTCGGGGATCTCGATTGCTTATGGATTTTCGAAATTCATCATGGGTTCGGTATCGGATCGCTCG
AATCCGCGCGTTTTCCTGCCCGCAGGTTTGATTCTGGCGGCGGCAGTGATGTTGTTTATGGGCTTTGTGCCATGGGCGACGTCGAGCATT
GCGGTGATGTTTGTACTGTTGTTCCTCTGCGGTTGGTTCCAGGGGATGGGGTGGCCGCCGTGTGGTCGTACTATGGTGCACTGGTGGTCG
CAGAAAGAACGTGGCGGCATTGTGTCAGTGTGGAACTGTGCGCACAACGTCGGTGGTGGTATTCCGCCGCTGCTGTTCCTGCTGGGGATG
GCCTGGTTCAATGACTGGCATGCGGCGCTCTATATGCCTGCTTTCTGCGCCATTCTGGTGGCATTATTCGCCTTTGCGATGATGCGCGAT
ACCCCGCAATCCTGTGGCTTGCCGCCGATCGAAGAGTACAAAAATGATTATCCGGACGACTATAACGAAAAAGCGGAACAGGAGCTGACG
GCGAAGCAAATCTTCATGCAGTACGTACTGCCGAACAAACTGCTGTGGTATATCGCCATCGCCAACGTGTTCGTTTATCTGCTGCGTTAC
GGCATCCTCGACTGGTCACCGACTTATCTGAAAGAGGTTAAGCATTTCGCGCTAGATAAATCCTCCTGGGCCTACTTCCTTTATGAATAT
GCAGGTATTCCGGGCACTCTGCTGTGCGGCTGGATGTCGGATAAAGTCTTCCGTGGCAACCGTGGGGCAACCGGCGTTTTCTTTATGACA
CTGGTGACCATCGCGACTATCGTTTACTGGATGAACCCGGCAGGTAACCCAACCGTCGATATGATTTGTATGATTGTTATCGGCTTCCTG
ATCTACGGTCCTGTGATGCTGATCGGTCTGCATGCGCTGGAACTGGCACCGAAAAAAGCGGCAGGTACGGCAGCGGGCTTTACCGGGCTG
TTTGGTTACCTGGGCGGTTCGGTGGCGGCGAGCGCGATTGTTGGCTACACCGTGGACTTCTTCGGCTGGGATGGCGGCTTTATGGTAATG
ATTGGCGGCAGCATTCTGGCGGTTATCTTGTTGATTGTTGTGATGATTGGCGAAAAACGTCGCCATGAACAATTACTGCAAGAACGCAAC
GGAGGCTAA

Curator Acknowledgements
Curator Description Most Recent Edit