Investigation of the Kinetics of Tet(O)-mediated Tetracycline Resistance

  • Author / Creator
    Li, Jun
  • Widespread tetracycline resistance (TcR) has limited the clinical use of Tc for the treatment of bacterial infections. Tet(O) protein is present in many bacteria and is the major transmissible TcR determinant in Campylobacter jejuni, a common cause of acute bacterial diarrhea worldwide. Tet(O) protects ribosomes against the inhibition of protein synthesis by Tc. Tet(O) binds to the ribosome at a similar site as EF-G, a structural homologue of Tet(O) with GTPase activity that is required for protein elongation. EF-G interfered with the kinetics of Tet(O)-mediated Tc release suggesting that EF-G competes with Tet(O) for ribosome binding. Indirect assessment of EF-G and Tet(O) binding to 70S ribosomes by GTP hydrolysis was unable to clearly demonstrate competition for binding. This thesis contributed to the further understanding of the kinetics of Tc release by Tet(O), and may facilitate the development of novel strategies to overcome Tet(O)-mediated TcR in bacteria which cause human infections.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medical Sciences - Laboratory Medicine and Pathology
  • Supervisor / co-supervisor and their department(s)
    • Monika Keelan (Laboratory Medicine and Pathology)
  • Examining committee members and their departments
    • Richard Fahlman (Biochemistry)
    • Jeff Fuller (Laboratory Medicine and Pathology)
    • Michael Gänzle (Agricultural, Food and Nutritional Sciences)