Protein glycosylation, LPS, and peptidoglycan: three pathways, many possibilities

Seminar

Title: Protein glycosylation, LPS, and peptidoglycan: three pathways, many possibilities

Speaker: Mario F. Feldman

Affiliation: Departments of Biological Sciences and Chemistry, Alberta Ingenuity Centre for Carbohydrate Science, University of Alberta, Edmonton, Alberta, Canada

Host: Jaime Mota-Infection Biology Laboratory

Abstract:  

Peptidoglycan (PG) and lipopolysaccharide (LPS), as well as some glycoproteins, are glycoconjugates synthesized by three independent but parallel pathways in Gram negative bacteria. The synthesis of these molecules start at the cytoplasm, use undecaprenylpyrophosphate (Und-PP) as lipid carrier, and flippases are involved in translocation of the building blocks to the periplasm, where the final steps of the assembly of the structures take place. The general N-glycosylation system of Campylobacter jejuni and pilin O-glycosylation in Neisseria meningitidis (Nm) follow this pathway.

 We have engineered E. coli cells to study the substrate specificity of PglL, the oligosaccharyltransferase involved in pilin glycosylation in Nm. We have found that these pathways can converge, as PglL is able to transfer glycans derived from LPS and PG biosynthesis to pilin.  Transfer of a PG subunit to a protein represents a previously unknown posttranslational modification. The promising applications of PglL for glycoconjugate vaccine development will be discussed.

 In a different set of experiments, we have elucidated the pathway leading to LPS synthesis of Helicobacter pylori. Surprisingly, H. pylori employs a novel pathway that makes use of a flippase that, in C. jejuni, plays a role in protein N-glycosylation. Thus, once more, LPS and protein glycosylation routes intersect, suggesting a common evolutionary origin for these processes in Gram negative bacteria.

Speaker Short Biography

For more information, please see http://www.biology.ualberta.ca/faculty/mario_feldman/