title: Relation between tetR and tetA expression in tetracycline resistant Escherichia coli.
abstract: BACKGROUND
  Tetracyclines are among the most used antibiotics in livestock worldwide. Resistance is widely disseminated in Escherichia coli, where it is generally mediated by tetracycline efflux pumps, such as TetA. Expression of tetracycline efflux pumps is tightly controlled by the repressor TetR, which has been shown to be tetracycline-responsive at sub-MIC tetracycline concentrations. The objective of this study was to investigate the effects of increasing tetracycline concentrations on the growth of TetA-producing E. coli, and to determine how expression of tetA and tetR related to each other in different growth phases in the presence of tetracycline.
  
  
  RESULTS
  A tetracycline resistant E. coli strain containing tetA and tetR on the chromosome was constructed and cultured in the presence of increasing concentrations of tetracycline. Expression of tetR and tetA was measured at four time points in different growth phases by quantitative real-time PCR. The TetA-producing E. coli exhibited prolonged lag phase with increasing concentrations of tetracycline, while expression of tetA and tetR increased and decreased, respectively, with increasing tetracycline concentration. The levels of tetA and tetR mRNA varied depending on growth phase, resulting in a gradual decrease of the tetA/tetR ratio from approximately 4 in the lag phase to approximately 2 in the stationary phase.
  
  
  CONCLUSIONS
  This study shows that the expression of tetR and tetA is tetracycline concentration- and growth phase-dependent, contributing to improved understanding of the relationships between E. coli growth, tetracycline exposure and expression of tetracycline resistance.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, C, Denmark.
authors.forename: Thea S B
authors.initials: TS
authors.lastname: Møller
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Overgaard
authors.affiliation: Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, C, Denmark.
authors.forename: Søren S
authors.initials: SS
authors.lastname: Nielsen
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, C, Denmark.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bortolaia
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.|Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Morten O A
authors.initials: MO
authors.lastname: Sommer
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, C, Denmark.
authors.forename: Luca
authors.initials: L
authors.lastname: Guardabassi
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, C, Denmark. jeo@sund.ku.dk.
authors.forename: John E
authors.initials: JE
authors.lastname: Olsen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology*; D013753:Tetracycline Resistance
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D013752:Tetracycline
keywords: Antimicrobial resistance; TetA; TetR; Tetracycline; Tetracycline resistance