|Title:||Genetic Basis for O-antigen Diversity in Escherichia coli and Salmonella enterica|
|Publisher:||University of Sydney.|
Faculty of Science.
|Abstract:||Cell-surface polysaccharide forms the outermost layer of many important groups of pathogens, and serves as an important virulence factor that interacts with the host immune system. These polysaccharides maintain very high levels of structural diversity, and in the case of O antigen, over 186 forms are known in Escherichia coli, 46 in Salmonella enterica, and about 200 in Vibrio cholerae, many of which consist of repeat units of three to eight sugars. Such structural diversity is largely attributed to the genetic diversity of O-antigen gene clusters, as demonstrated by the large number of sequences now available for glycosyltransferase genes, as well as wzx and wzy genes. Most bacterial cell-surface polysaccharides are synthesized by the Wzx/Wzy dependent pathway. The synthesis begins with the assembly of repeat units on the cytoplasmic side of the inner membrane on membrane buried lipid carriers. The function of the Wzx translocase is to transport the repeat units to the periplasmic side, where the Und-PP linked repeat units can be polymerized by the Wzy polymerase into polymers consists of many repeat units, and for O antigen, the finalized polymer is incorporated into lipopolysaccharide. This study sought to explore the genetic basis for O-antigen diversity, using the two paradigm species for bacterial cell-surface polysaccharide research, E. coli and S. enterica. In the process, this study established: 1/ the functional understanding of the wbaK gene, the last functionally uncharacterized gene of the galactose-initiated S. enterica O-antigen gene clusters; and 2/ membrane translocation by Wzx translocases of the lipid carrier linked repeat units involves specific substrate recognition, which links the diversity of cell-surface polysaccharide repeat-unit structures to the sequence variation of Wzx translocases. Overall, the project gives an insight into the genetic basis for the synthesis of complex cell-surface polysaccharides.|
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|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|hong_y_thesis.pdf||PhD Thesis||11.28 MB||Adobe PDF|
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