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http://hdl.handle.net/11375/21600
Title: | Construction of Cell-based Antibiotic Resistance Arrays |
Authors: | Sutherland, Arlene |
Advisor: | Wright, G. D. |
Department: | Biblical Studies, Religion |
Keywords: | Cell-based;Antibiotic Resistance;Resistance Arrays;health care |
Publication Date: | Sep-2008 |
Abstract: | As the problem of resistance increases in the current health care system, new solutions to this problem are not emerging at a similar rate. The ability to discover novel antibiotics, and modify existing antibiotics, is competing with highly evolving resistance profiles. An alternate solution to this problem may be to search for inhibitors of these resistance mechanisms and pairing them with current antibiotics. Proof of this hypothesis lies in the great success of P-lactamase inhibitors already in the clinic. Inhibitors may be created using synthetic methods, however searching for inhibitors found in the natural environment may lead to a greater success. For example, bacteria in their natural setting must cope with constant exposure to antibiotics secreted by both themselves and by other species. As well, bacteria must be able to handle encounters with other species that are resistant to their own defense mechanisms. With this in consideration, it is possible that these bacteria have already established an ability to challenge resistance encountered in their own environment, such as through the secretion of compounds that inhibit these mechanisms. Screening of such inhibitors can be done against purified resistance elements or via cell-based screens with resistant bacteria. The focus of this research was to develop expression systems which contain inducible antibiotic resistance genes to be used for whole-cell screening for inhibitors of antibiotic resistance. The expression systems studied were pSWEET, for use in the Gram positive bacterium Bacillus subtilis, and pETcoco, for use in the Gram negative bacterium Escherichia coli. It was found that the pSWEET expression system integrated into the B. subtilis chromosome at unspecified locations and was not an ideal system for the proposed screen. pET coco holds promise as a suitable expression system but at this point in time it requires further examination to ensure plasmid stability and reproducibility of results. Therefore further examination of these two systems is needed if they are to be used in a screen for inhibitors, and a search for substitute systems must be undertaken. |
URI: | http://hdl.handle.net/11375/21600 |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Sutherland_Arlene_D_2008Sept_Masters.pdf | 5.67 MB | Adobe PDF | View/Open |
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