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Title: Beyond gangliosides: Multiple forms of glycan mimicry exhibited by Campylobacter jejuni in its lipooligosaccharide (LOS)

Author
item Houliston, R - National Research Council - Canada
item Vinogradov, E - National Research Council - Canada
item Li, J - National Research Council - Canada
item Dzieciatkowska, M - National Research Council - Canada
item St.michael, F - National Research Council - Canada
item Karwaski, M - National Research Council - Canada
item Brochu, D - National Research Council - Canada
item Jarrell, H - National Research Council - Canada
item Parker, Craig
item Yuki, N - National University Of Singapore
item Mandrell, Robert
item Gilbert, M - National Research Council - Canada

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2010
Publication Date: 1/21/2011
Publication URL: http://www.ncbi.nlm.nih.gov/pubmed/21257763 DOI: M10.181750[pii]10.1074/jbc.M110.19750
Citation: Houliston, R.S., Vinogradov, E., Li, J., Dzieciatkowska, M., St.Michael, F., Karwaski, M., Brochu, D., Jarrell, H.C., Parker, C., Yuki, N., Mandrell, R.E., Gilbert, M.E. 2011. Beyond gangliosides: Multiple forms of glycan mimicry exhibited by Campylobacter jejuni in its lipooligosaccharide (LOS). Journal of Biological Chemistry. 286:12361-12370.

Interpretive Summary: The food-borne pathogen Campylobacter jejuni is well known for exhibiting ganglioside mimics as part of their surface called lipooligosaccharide (LOS), which have been implicated in triggering the neurologically debilitating Guillain-Barré syndrome (GBS). We now confirm that this pathogen is also capable of synthesizing a much broader spectrum of human glycolipid/glycoprotein mimics within its LOS. P-blood group and paragloboside (lacto-N-neotetraose) antigen mimicry is exhibited by RM1221, a strain isolated from a poultry source. RM1503, also a gastroenteritis-associated strain, expresses lacto-N-biose and sialyl-Lewis c units, the latter known as the pancreatic tumor-associated antigen, DU-PAN-2 (or LSTa). C. jejuni GC149, a GBS-associated strain, expresses an unusual sialic acid-containing hybrid oligosaccharide with similarity to both ganglio and Pk antigens and can, through phase variation of its LOS biosynthesis genes, display GT1a or GD3 ganglioside mimics. We have identified glycosyltransferases involved in the synthesis of multiple mimic types, with LOS structural diversity achieved through evolving allelic substrate specificity.

Technical Abstract: Campylobacter jejuni is well known for synthesizing ganglioside mimics within the glycan component of its lipooligosaccharide (LOS), which have been implicated in triggering Guillain-Barré syndrome (GBS). We now confirm that this pathogen is capable of synthesizing a much broader spectrum of host glycolipid/glycoprotein mimics within its LOS. P-blood group and paragloboside (lacto-N-neotetraose) antigen mimicry is exhibited by RM1221, a strain isolated from a poultry source. RM1503, also a gastroenteritis-associated strain, expresses lacto-N-biose and sialyl-Lewis c units, the latter known as the pancreatic tumor-associated antigen, DU-PAN-2 (or LSTa). C. jejuni GC149, a GBS-associated strain, expresses an unusual sialic acid-containing hybrid oligosaccharide with similarity to both ganglio and Pk antigens and can, through phase variation of its LOS biosynthesis genes, display GT1a or GD3 ganglioside mimics. We have identified glycosyltransferases involved in the synthesis of multiple mimic types, with LOS structural diversity achieved through evolving allelic substrate specificity.