Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Carole Creuzenet

Second Advisor

Dr. Wayne Flintoff

Third Advisor

Dr. David Heinrichs

Abstract

Glycoproteins are important for the virulence of Campylobacter jejuni. The enzymes involved in protein glycosylation could provide new therapeutic targets. Two such proteins are Cjll23c, a putative acetyltransferase and Cj 1319, a putative GDP-mannose dehydratase encoded by the N- and O-linked protein glycosylation loci in C. jejuni, respectively. We show that Cjll23c is responsible for the synthesis of UDP- diacetamidobacillosamine. We also show that Cj 1123c can N-acetylate the O- glycosylation pathway intermediate, UDP-4-amino-4,6-dideoxy-AltNAc, accommodate different acyl donors and O-acetylate UDP-GlcNAc, thereby generating novel sugars. We demonstrate that Cj 1319 converts GDP-mannose with low conversion efficiency, suggesting that it is not the ideal substrate. We observed a buildup of a sugar-nucleotide within a Cjl319~ deficient strain that may represent the true substrate of Cj 1319. Identifying this substrate will elucidate the preferred biochemical activity of Cj 1319 and its biological role in C. jejuni. As these enzymes are involved in novel sugar biosynthesis, they could be applied as glycoengineering tools.

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