Bacterial biofilms are surface associated colonies that are of considerable concern and interest to industry, medicine and research. They are resistant to antibiotics, their host’s defences and are able to survive under harsh conditions. Biofilm formation in many bacterial strains are dependent on the production of a polysaccharide intercellular adhesion (PIA), a beta-(1-->6)-N-acetylglucosamine polymer. Vaccines derived from biologically isolated PIA have shown efficacy against clinically isolated strains of E. coli and pathogenic strains of S. aureus in animal models. Accordingly, chemically synthesized neoglycoconjugates based on PIA glycosides will be developed to serve as lead compounds for the development of new antibiotics as well as vaccines against biofilm dependent infections. Described in this thesis is a comprehensive study of the synthesis of PIA oligosaccharides and their deacetylated equivalents, the strategy for installing a stable linker on the free reducing oligosaccharide terminus and finally the conjugation to a model carrier protein for the development of potential neoglycoprotein vaccines.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17193 |
| Date | 24 February 2009 |
| Creators | Leung, Carmen |
| Contributors | Nitz, Mark |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
| Format | 1625218 bytes, application/pdf |
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