title: Integron-Associated DfrB4, a Previously Uncharacterized Member of the Trimethoprim-Resistant Dihydrofolate Reductase B Family, Is a Clinically Identified Emergent Source of Antibiotic Resistance.
abstract: Whole-genome sequencing of trimethoprim-resistantEscherichia coliclinical isolates identified a member of the trimethoprim-resistant type II dihydrofolate reductase gene family (dfrB). ThedfrB4gene was located within a class I integron flanked by multiple resistance genes. This arrangement was previously reported in a 130.6-kb multiresistance plasmid. The DfrB4 protein conferred a >2,000-fold increased trimethoprim resistance on overexpression inE. coliOur results are consistent with the finding thatdfrB4contributes to clinical trimethoprim resistance.
authors.affiliation: Département de biochimie, Université de Montréal, C.P. 6128,Succursale Centre-ville, Montréal, Québec, Canada.|CGCC, Center in Green Chemistry and Catalysis, Montréal, Québec, Canada.|PROTEO, Québec Network for Protein Function, Engineering and Applications, Québec, Québec, Canada.
authors.forename: Jacynthe L
authors.initials: JL
authors.lastname: Toulouse
authors.affiliation: Devil's Staircase Consulting, North Vancouver, British Columbia, Canada.
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Edens
authors.affiliation: Département de biochimie, Université de Montréal, C.P. 6128,Succursale Centre-ville, Montréal, Québec, Canada.|CGCC, Center in Green Chemistry and Catalysis, Montréal, Québec, Canada.|PROTEO, Québec Network for Protein Function, Engineering and Applications, Québec, Québec, Canada.
authors.forename: Lorea
authors.initials: L
authors.lastname: Alejaldre
authors.affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Amee R
authors.initials: AR
authors.lastname: Manges
authors.affiliation: Département de biochimie, Université de Montréal, C.P. 6128,Succursale Centre-ville, Montréal, Québec, Canada joelle.pelletier@umontreal.ca.|CGCC, Center in Green Chemistry and Catalysis, Montréal, Québec, Canada.|PROTEO, Québec Network for Protein Function, Engineering and Applications, Québec, Québec, Canada.|Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada.
authors.forename: Joelle N
authors.initials: JN
authors.lastname: Pelletier
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000235:genetics*; D006801:Humans; D032023:Integrons / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014295:Trimethoprim / Q000494:pharmacology*; D014296:Trimethoprim Resistance / Q000235:genetics*; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000892:Anti-Infective Agents, Urinary; C000625759:DfrB4 protein, E coli; D029968:Escherichia coli Proteins; D014295:Trimethoprim; C098921:dihydrofolate reductase type II; D013762:Tetrahydrofolate Dehydrogenase
keywords: E. coli clinical isolates; antibiotic-resistant genes; class I integron; dfrB4; trimethoprim resistance; type II dihydrofolate reductase; urinary tract infection