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首页> 外文期刊>Infection and immunity >Toxoid of Pseudomonas aeruginosa exotoxin A generated by deletion of an active-site residue.
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Toxoid of Pseudomonas aeruginosa exotoxin A generated by deletion of an active-site residue.

机译：通过缺失活性位点残基产生的铜绿假单胞菌外毒素A的类毒素。

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摘要

Glutamic acid-553 of Pseudomonas aeruginosa exotoxin A (ETA), identified previously as an active-site residue, was deleted by oligonucleotide-directed mutagenesis of the cloned toxin gene in Escherichia coli. The purified mutant toxin was stable, fully immunoreactive, and capable of blocking toxin receptors. ADP-ribosyltransferase and cytotoxic activities were at least 10(6)-fold lower than those of wild-type ETA, and injection of mice with 50 micrograms (equivalent to 400 lethal doses of ETA) produced no ill effects. The mutant toxin elicited high levels of neutralizing anti-ETA antibodies in mice, which protected against a challenge with 100 micrograms of authentic ETA (greater than 600 lethal doses). The mutant protein has the attributes of a toxoid and may be useful as a component of vaccines for individuals at risk for infection by P. aeruginosa.
机译：铜绿假单胞菌外毒素A（ETA）的谷氨酸553（先前已鉴定为活性位点残基）通过在大肠杆菌中进行寡核苷酸定向诱变来克隆克隆的毒素基因而被删除。纯化的突变毒素是稳定的，完全免疫反应的，并且能够阻断毒素受体。 ADP-核糖基转移酶和细胞毒性活性比野生型ETA至少低10（6）倍，并且给小鼠注射50微克（相当于400致死剂量的ETA）不会产生不良影响。突变毒素在小鼠中引起高水平的中和性抗ETA抗体，可抵抗100微克的真实ETA（大于600致死剂量）的攻击。突变蛋白具有类毒素的特性，可以用作有铜绿假单胞菌感染风险的个体的疫苗组分。

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