Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin

Emma Byres, Adrienne W. Paton, James C. Paton, Jonas C. Löfling, David F. Smith, Matthew C. J. Wilce, Ursula M. Talbot, Damien C. Chong, Hai Yu, Shengshu Huang, Xi Chen, Nissi M. Varki, Ajit Varki (), Jamie Rossjohn () and Travis Beddoe ()
Additional contact information
Emma Byres: Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia
Adrienne W. Paton: School of Molecular and Biomedical Science, University of Adelaide
James C. Paton: School of Molecular and Biomedical Science, University of Adelaide
Jonas C. Löfling: Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687, USA
David F. Smith: Protein-Carbohydrate Interaction Core H, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Matthew C. J. Wilce: Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia
Ursula M. Talbot: School of Molecular and Biomedical Science, University of Adelaide
Damien C. Chong: School of Molecular and Biomedical Science, University of Adelaide
Hai Yu: University of California, Davis, California 95616, USA
Shengshu Huang: University of California, Davis, California 95616, USA
Xi Chen: University of California, Davis, California 95616, USA
Nissi M. Varki: Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687, USA
Ajit Varki: Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687, USA
Jamie Rossjohn: Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia
Travis Beddoe: Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia

Nature, 2008, vol. 456, issue 7222, 648-652

Abstract: Double exposure Shiga toxigenic Escherichia coli causes severe gastrointestinal disease, in part mediated by subtilase cytotoxin. The B subunit of this toxin is now shown to have high affinity for glycans containing N-glycolylneuraminic acid, a saccharide that is not synthesized by humans. Instead it is ingested as part of the diet, in red meat and dairy products and subsequently incorporated into intestinal and kidney tissue. Ironically, red meat and dairy products, rich sources of N-glycolylneuraminic acid, are also the foods most commonly contaminated with the toxic bacteria. So through dietary choices, humans may both expose themselves to a pathogen and simultaneously become more susceptible to it as their tissues are sensitized to a key virulence factor.

Date: 2008
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DOI: 10.1038/nature07428

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