Molecule Information

General Information of the Molecule (ID: Mol00899)

• Name: Dihydrofolate reductase (DHFR) ,Escherichia coli
• Synonyms: dfrA; dhfr; dhfr12; dhfrA12; dhfrXII; AOY10_00067; B6R12_004225; B6R12_005492; B6R15_004946; B6R15_005525; BANRA_05018; BANRA_05550; BHS81_30685; BJI68_09275; BJJ90_26820; BK292_28535; BK383_28330; BVL39_27785; CA593_26965; CR538_27010; CR538_27775; CR539_26880; D9C02_25135; E2117_19040; E2133_22650; E4K51_27155; E5P24_23220; E5P25_24335; E5S34_22245; EA239_25350; EI021_22810; EIZ93_23115; ELT27_22805; ELT29_23875; ELT56_25010; ELU90_23320; ELV08_25350; ELX61_23120; ELX85_17445; F3N40_24870; F3N40_27900; FTV93_26310; G5603_27160; G5632_22460; HHH44_004744; HHH44_005252; HMU48_23540; HMU48_30935; HNC36_27120; HNC36_29310; HNC99_24940; HNC99_29620; HND12_29345; HND12_30765; HND12_30780; HND12_30795; HND12_30810; HVX16_27030; HVX16_27860; J0541_005704; J0541_005934; NDM1Dok01_N0147; RCS28_PI0034; RCS40_P0057; RCS51_P0085; RCS55_PI0020; SAMEA3472044_03632; SAMEA3472080_05518; TUM18780_18810
• Molecule Type: Protein
• Gene Name: dfrA12
• Gene ID: 61419540
• Sequence:
  MNSESVRIYLVAAMGANRVIGNGPNIPWKIPGEQKIFRRLTEGKVVVMGRKTFESIGKPL
  PNRHTLVISRQANYRATGCVVVSTLSHAIALASELGNELYVAGGAEIYTLALPHAHGVFL
  SEVHQTFEGDAFFPMLNETEFELVSTETIQAVIPYTHSVYARRNG
• Function: Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
• Uniprot ID: Q79DQ2_ECOLX

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 6 drug(s) in total

Amikacin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary tract infection [1]

• Sensitive Disease: Urinary tract infection [ICD-11: GC08.1]
• Sensitive Drug: Amikacin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: Escherichia coli serogroup O77; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.

Ampicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary tract infection [1]

• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Resistant Drug: Ampicillin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: Escherichia coli serogroup O77; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary tract infection [1]

• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: Escherichia coli serogroup O77; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.

Co-trimoxazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Urinary tract infection [1]

• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: Escherichia coli serogroup O77; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.

Gentamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Urinary tract infection [1]

• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Resistant Drug: Gentamicin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: Escherichia coli serogroup O77; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Microdilution method assay
• Mechanism Description: All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.

Trimethoprim

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Escherichia coli infection [2]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Trimethoprim
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli Co227; 562
• In Vitro Model: Escherichia coli Co228; 562
• In Vitro Model: Escherichia coli Co232; 562
• In Vitro Model: Escherichia coli Co354; 562
• Experiment for Molecule Alteration: PCR; PCR-restriction fragment length polymorphism analysis; Sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Multiple-antibiotic-resistant phenotype is associated with gene mutation and mar locus regulation.

References

• Ref 1: Global spread of mobile antimicrobial drug resistance determinants in human and animal Escherichia coli and Salmonella strains causing community-acquired infections. Clin Infect Dis. 2009 Aug 1;49(3):365-71. doi: 10.1086/600301.
• Ref 2: Mechanisms of resistance in multiple-antibiotic-resistant Escherichia coli strains of human, animal, and food origins. Antimicrob Agents Chemother. 2004 Oct;48(10):3996-4001. doi: 10.1128/AAC.48.10.3996-4001.2004.