人們常說，紅肉吃多了對健康有害。一項新的研究表明，這話確實有它的道理。美國科學家近日首次發現，當某種細菌在人體中標靶一種特殊的分子時，就會導致食物中毒。而這種分子來自於牛羊肉等紅肉，並非人體自然產生。相關論文10月29日在線發表於《自然》（Nature）雜誌。
美國加州大學聖地亞哥分校的Ajit Varki和同事發現，一種名為subtilase細胞毒素的強力細菌毒素，能特異性地標靶表面具有某種非人類分子的人類細胞。這種分子名為N-羥乙酰神經氨酸（Neu5Gc），是一種多糖，人體不會自然產生。
subtilase細胞毒素由某些種類的大腸桿菌產生，會導致血性腹瀉和具有潛在致命性的溶血性尿毒症（HUS）。人類食用受汙染的紅肉後經常會受到感染。
Varki說：“諷刺的是，人類自己提升了自身患上疾病的風險，這些疾病來自含有某種大腸桿菌的受汙染紅肉或乳製品，因為它們含有高水平的Neu5Gc。Neu5Gc分子被吸收到人體中後，成為了大腸桿菌產生的毒素的靶標。”
研究人員在實驗中發現，Neu5Gc結合到人體的位點與毒素綁定相一致。Varki說：“當毒素綁定到非人類的Neu5Gc受體時，它能導致嚴重的食物中毒和其它症狀。”所以，研究人員強調，為了安全起見，人們需要食用適當烹煮的肉類和充分滅菌的乳製品。（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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