志賀毒素大腸桿菌能引起嚴(yán)重腸道疾病,，其致病機(jī)制部分是由枯草桿菌酶（subtilase）細(xì)胞毒素調(diào)控的,。
現(xiàn)在,，這種毒素的B-亞單元被發(fā)現(xiàn)對含有N-羥乙酰神經(jīng)氨酸的聚糖有很高親和力,。這種糖類不是由人體合成的，而是作為飲食（如紅肉和奶品等）一部分消化的,，隨后進(jìn)入小腸和腎臟組織,。
具有諷刺意味的是，紅肉和奶品（N-羥乙酰神經(jīng)氨酸的豐富來源）也是最常被有毒細(xì)菌污染的食物,。所以,，通過飲食選擇，人類可能會在將自己暴露于一種病原體的同時變得對其更加易感,，因為他們的身體組織已變得對一種關(guān)鍵毒性因子非常敏感,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 456, 648-652 (4 December 2008) | doi:10.1038/nature07428
Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin
Emma Byres1,6, Adrienne W. Paton2,6, James C. Paton2, Jonas C. L?fling3, David F. Smith4, Matthew C. J. Wilce1, Ursula M. Talbot2, Damien C. Chong2, Hai Yu5, Shengshu Huang5, Xi Chen5, Nissi M. Varki3, Ajit Varki3, Jamie Rossjohn1 & Travis Beddoe1
1 Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
2 School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia
3 Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687, USA
4 Protein-Carbohydrate Interaction Core H, Emory University School of Medicine, Atlanta, Georgia 30322, USA
5 Department of Chemistry, University of California, Davis, California 95616, USA
AB5 toxins comprise an A subunit that corrupts essential eukaryotic cell functions, and pentameric B subunits that direct target-cell uptake after binding surface glycans. Subtilase cytotoxin (SubAB) is an AB5 toxin secreted by Shiga toxigenic Escherichia coli (STEC)1, which causes serious gastrointestinal disease in humans2. SubAB causes haemolytic uraemic syndrome-like pathology in mice3 through SubA-mediated cleavage of BiP/GRP78, an essential endoplasmic reticulum chaperone4. Here we show that SubB has a strong preference for glycans terminating in the sialic acidN-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans. Structures of SubB–Neu5Gc complexes revealed the basis for this specificity, and mutagenesis of key SubB residues abrogated in vitro glycan recognition, cell binding and cytotoxicity. SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human-like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite lack of Neu5Gc biosynthesis in humans, assimilation of dietary Neu5Gc creates high-affinity receptors on human gut epithelia and kidney vasculature. This, and the lack of Neu5Gc-containing body fluid competitors in humans, confers susceptibility to the gastrointestinal and systemic toxicities of SubAB. Ironically, foods rich in Neu5Gc are the most common source of STEC contamination. Thus a bacterial toxin's receptor is generated by metabolic incorporation of an exogenous factor derived from food.
