Escherichia coli GlpT with mutation conferring resistance to fosfomycin

Accession ARO:3003889
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 FamilyGlpT
Drug Classfosfomycin
Resistance Mechanismantibiotic target alteration
Classification9 ontology terms | Show
Parent Term(s)3 ontology terms | Show
+ confers_resistance_to_antibiotic fosfomycin [Drug Class]
+ antibiotic resistant gene variant or mutant
+ 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 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 (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGS
Citrobacter amalonaticus100%0%100%
Citrobacter freundii100%0%93.02%
Citrobacter koseri100%0%95.83%
Citrobacter youngae100%0%75%
Enterobacter cloacae0%0%0.45%
Enterobacter kobei0%0%1.56%
Enterococcus faecium0%0%0.21%
Escherichia coli9.66%0%76.25%
Klebsiella oxytoca0%0%1.87%
Klebsiella pneumoniae0%0%0%
Morganella morganii0%0%2.38%
Salmonella enterica100%0%98.95%
Serratia marcescens24.32%0%25.58%
Shigella dysenteriae100%0%100%
Shigella flexneri100%0%99.48%
Shigella sonnei100%0%96.16%
Vibrio parahaemolyticus0%0%0.17%
Yersinia enterocolitica0%0%0.65%
Show Perfect Only


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): 850

PMID: 20071153E448K E448K, G302D E448K, G33R E448K, Q444E, E443Q, L297F

>gb|CDJ72593|-|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|-|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