Deletion or substitution of conserved amino acid residues at the tip of the domain IV of Tet(O) impairs tetracycline resistance

• Author / Creator

  Mukherjee, Oindrila

• Resistance to tetracycline (Tc), an inhibitor of protein synthesis, decreases its effectiveness for the treatment of bacterial infections. Tc resistance (TcR) can be mediated by the ribosomal protection protein, Tet(O), which was first reported in Campylobacter jejuni, a cause of bacterial diarrhea worldwide. Tet(O) confers TcR by mediating Tc release from 70S ribosomes, thus restoring protein synthesis. Tet(O) is widely distributed in a variety of bacterial genera, restraining the clinical use of Tc. This thesis is the first investigation into the role of the conserved set of amino acid residues, YSPVST, occupying positions 507-512 at the tip of domain IV of Tet(O). Impaired Tc release from 70S ribosomes observed with Tet(O)mutants lacking one or more of these conserved residues suggests residues at positions 509-512 play a role in Tet(O)-mediated TcR. This study provides insight into the molecular mechanism of TcR, which is essential for the development of novel therapeutics.

• Subjects / Keywords

  • Tet(O)
  • Tetracycline
  • Resistance

• Graduation date

  Spring 2011

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3K43N

• 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.