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Structure and biosynthesis of capsular polysaccharides synthesized via ABC transporter-dependent processes

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dc.contributor.advisor Whitfield, Chris
dc.contributor.author Willis, Elizabeth
dc.date.accessioned 2013-09-07T18:23:03Z
dc.date.available 2013-09-07T18:23:03Z
dc.date.copyright 2013
dc.date.created 2013-08-23
dc.date.issued 2013-09-07
dc.identifier.uri http://hdl.handle.net/10214/7479
dc.description.abstract Bacterial capsules are important virulence factors for a number of different pathogens, including Escherichia coli, Neisseria meningitidis, Haemophilus influenzae, and Pasteurella multocida. Capsular polysaccharides (CPSs) synthesized via the ATP-binding cassette (ABC) transporter-dependent pathway protect these bacteria from complement-mediated killing and phagocytosis, and consist of long polysaccharide chains attached to the cell surface via a phospholipid. CPSs are synthesized on the cytoplasmic face of the inner membrane before transport to the cell surface. While the enzymes that synthesize the polysaccharide have been studied in detail, very little is known about the structure and biosynthesis of the phospholipid terminus. To determine the structure of the reducing terminal glycolipid, CPS from E. coli K1, K5, and N. meningitidis group B was purified using a novel strategy and its structure was determined by mass spectrometry, nuclear magnetic resonance and chemical methods. All three polysaccharides possess terminal lyso-phosphatidylglycerol, which is connected to the CPS repeat unit by a linker consisting of multiple 3-deoxy-D-manno-octulosonic acid (Kdo) residues, forming an alternating β-2,4/β-2,7-linked structure. In addition to describing its structure, the biosynthesis of the glycolipid terminus was also investigated. KpsC and KpsS are conserved proteins encoded in the capsule loci from different bacteria with ABC transporter-dependent capsule assembly pathways but have no previously assigned function. An in vitro assay was developed to characterize KpsSC activities, leading to the finding that they are the Kdo transferases responsible for synthesis of the poly-Kdo linker. This research has contributed significantly to the understanding of the structure and biosynthesis of capsular polysaccharides. en_US
dc.language.iso en en_US
dc.subject bacterial capsules en_US
dc.subject glycobiology en_US
dc.title Structure and biosynthesis of capsular polysaccharides synthesized via ABC transporter-dependent processes en_US
dc.type Thesis en_US
dc.degree.programme Molecular and Cellular Biology en_US
dc.degree.name Doctor of Philosophy en_US
dc.degree.department Department of Molecular and Cellular Biology en_US
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