Differentiation between structurally homologous Shiga 1 and Shiga 2 toxins by using synthetic glycoconjugates
Differentiation between structurally homologous Shiga 1 and Shiga 2 toxins by using synthetic glycoconjugates
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DOI：
10.1002/anie.200703680
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Iyer, Suri S.
中科院分区：
文献类型：
--
作者：
Kale, Ramesh R.;McGannon, Colleen M.;Iyer, Suri S.
滋贺毒素1和志贺毒素2（Stx 1和Stx 2）是大肠杆菌O 157：H7的主要毒力因子，已被列入生物威胁因子清单。[1]估计70000 E。coli O157：在美国，每年H7疾病病例中，10-15%发展为溶血性尿毒综合征（HUS）; 3-5%在疾病的急性期死亡;并且相当数量的人遭受脑损伤和肾衰竭。[2]志贺毒素介导的HUS的治疗仍然主要是支持性的，因为据报道腹泻后抗生素治疗会增强毒素的产生和HUS的进展。[3]合成毒素中和剂已被证明对受影响的患者无效，但如果能早期诊断，则可用作药物。[4-6]此外，溶原性噬菌体上Stx基因的存在[7]允许Stx容易地传播到无害的E.大肠杆菌和其他肠道细菌物种，使其成为一个严重的新兴威胁人类。[8]滋贺毒素是毒素AB 5家族的成员。A亚基具有酶活性，从28 S核糖体RNA上切割一个腺嘌呤残基，使核糖体不能合成蛋白质。B或结合亚基是一种同五聚体，其结合细胞表面脂筏中的神经酰胺三己糖苷（Gb 3），并最终将A亚基递送至其细胞质靶标。滋贺毒素的两种主要抗原变体Stx 1和Stx 2具有55%的氨基酸同源性。通过使用表面等离子体共振光谱观察到对Gb 3的亲和力的差异;
Shiga toxins 1 and 2 (Stx1 and Stx2) are major virulence factors of Escherichia coli O157: H7 and have been included on the list of Select Biothreat Agents.[1] Of the estimated 70 000 E. coli O157: H7 cases of disease per year in the United States, 10–15% develop hemolytic uremic syndrome (HUS); 3–5% succumb during the acute phase of the disease; and an equivalent number suffer brain damage and renal failure.[2] Treatment of Shiga-toxin-mediated HUS remains primarily supportive, as postdiarrheal antibiotic treatment is reported to enhance toxin production and progression of HUS.[3] Synthetic toxin neutralizers have proven to be ineffective in affected patients, but could be useful as prophylactics if diagnosis can be made early.[4–6] Furthermore, the presence of Stx genes on the lysogenic bacteriophage [7] allows facile transmission of Stx onto harmless serotypes of E. coli and other enteric bacterial species, making it a serious emerging threat to humans.[8]Shiga toxin is a member of the AB5 family of toxins. The A subunit is enzymatically active and cleaves a single adenine residue from the 28S ribosomal RNA, rendering the ribosome incapable of protein synthesis. The B, or binding, subunit is a homopentamer that binds to globotriaosylceramide (Gb3) in lipid rafts on the cell surface and ultimately delivers the A subunit to its cytoplasmic target. The two major antigenic variants of Shiga toxin, Stx1 and Stx2, share 55% amino acid homology. Differences in affinity for Gb3 were observed by using surface plasmon resonance spectroscopy; the affinities