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.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1150 |
| Date | 11 1900 |
| Creators | Li, Jun |
| Contributors | Monika Keelan (Laboratory Medicine and Pathology), Jeff Fuller (Laboratory Medicine and Pathology), Richard Fahlman (Biochemistry), Michael Gnzle (Agricultural, Food and Nutritional Sciences) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 3410209 bytes, application/pdf |
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