原标题：Nature：吃红肉易向人体牵入“特洛伊木马”
人们常说，红肉吃多了对健康有害。一项新的研究表明，这话确实有它的道理。美国科学家近日首次发现，当某种细菌在人体中标靶一种特殊的分子时，就会导致食物中毒。而这种分子来自于牛羊肉等红肉，并非人体自然产生。相关论文10月29日在线发表于《自然》（Nature）杂志。
美国加州大学圣地亚哥分校的Ajit Varki和同事发现，一种名为subtilase细胞毒素的强力细菌毒素，能特异性地标靶表面具有某种非人类分子的人类细胞。这种分子名为N-羟乙酰神经氨酸（Neu5Gc），是一种多糖，人体不会自然产生。
subtilase细胞毒素由某些种类的大肠杆菌产生，会导致血性腹泻和具有潜在致命性的溶血性尿毒症（HUS）。人类食用受污染的红肉后经常会受到感染。
Varki说：“讽刺的是，人类自己提升了自身患上疾病的风险，这些疾病来自含有某种大肠杆菌的受污染红肉或乳制品，因为它们含有高水平的Neu5Gc。Neu5Gc分子被吸收到人体中后，成为了大肠杆菌产生的毒素的靶标。”
研究人员在实验中发现，Neu5Gc结合到人体的位点与毒素绑定相一致。Varki说：“当毒素绑定到非人类的Neu5Gc受体时，它能导致严重的食物中毒和其它症状。”所以，研究人员强调，为了安全起见，人们需要食用适当烹煮的肉类和充分灭菌的乳制品。（生物谷Bioon.com）
Nature，doi:10.1038/nature07428，Emma Byres，Ajit Varki
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, Australia2 School of Molecular and Biomedical Science, University of Adelaide, South Australia 5005, Australia3 Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California 92093-0687, USA4 Protein-Carbohydrate Interaction Core H, Emory University School of Medicine, Atlanta, Georgia 30322, USA5 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 acid N-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.
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