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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1731 |
| Date | 06 1900 |
| Creators | Mukherjee, Oindrila |
| Contributors | Keelan, Monika (Laboratory Medicine and Pathology), Tyrrell, Greg (Laboratory Medicine and Pathology), Fahlman, Richard (Department of Biochemistry), Pukatzki, Stefan (Medical Microbiology and Immunology) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Format | 5842669 bytes, application/pdf |
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