The overexpression of efflux transporters is deemed to be one of the important mechanisms that contribute to Multidrug Resistance (MDR). In this dissertation, three transporters of significance were studied, the Breast Cancer Resistance Protein (BCRP/ABCG2) in a variety of cancer cells, the mtrCDE transporter from Neisseria gonorrhoeae, and the acrAB-tolC transporter from Escherichia coli. It is well known that the overexpression of BCRP in cancer cells results in these cells being resistant to the effects of many chemotherapeutics. This results in multidrug resistance for this cancer because of the fact that BCRP can transport many different types of chemotherapeutics out of the cell, making them ineffective in stopping the cancer’s growth. Because of a lack of therapeutic alternative, more investigations on the mechanisms of MDR in BCRP drug transport would be vital for drug discovery in the future. Furthermore, the homologous mtrCDE and acrAB-tolC transporters from bacteria, two members of the RND (resistance nodulation division) superfamily, share similarities in some aspects to each other and to BCRP in the sense that overexpression of these bacterial transporters also leads to MDR or in these bacterial cases, Multiple Antibiotic Resistance. Studying both mtrCDE and acrAB-tolC transporters and screening for potential inhibitors would be helpful for finding alternative methods to decrease bacterial MDR, since inhibition of these transporters would re-sensitize the cells to antibiotic treatments.
Dr. John G. Wise
Biological Sciences, General, Cell Biology, Molecular Biology, Microbiology
Number of Pages
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Zhao, Hang, "Dynamics and Inhibition of ABC and RND Transporters Associated with Multidrug Resistances in Cancer and Pathogenic Bacteria" (2023). Biological Sciences Theses and Dissertations. 21.
Available for download on Friday, December 06, 2024