Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin A by synthetic peptides

Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin A by synthetic peptides
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DOI:
10.1016/j.peptides.2012.08.013
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发表时间:
2012-11-01
期刊:
影响因子:
3
通讯作者:
Nakane, Akio
Nakane, Akio
中科院分区:
医学3区
文献类型:
--
作者:
Maina, Edward K.;Hu, Dong-Liang;Nakane, Akio

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金黄色葡萄球菌是一种主要的人类病原体,产生不同类型的毒素。肠毒素A(SEA)是临床和食品相关菌株中最常见的类型。本研究的目的是估计SEA的功能区域,负责使用合成肽的呕吐和超抗原活性。合成了13个SEA特异性区域的合成肽,并研究了这些肽对SEA超抗原活性的影响,包括小鼠脾细胞产生干扰素-γ(IFN-γ)、SEA诱导小鼠致死性休克、家麝鼩脾细胞增殖和鼩 鼩的催吐活性。用对应于SEA的区域21-40、35-50、81-100或161-180的合成肽预处理脾细胞显著抑制SEA诱导的IFN-γ产生和细胞增殖。这些肽也抑制SEA诱导的致死性休克。有趣的是,对应于区域21- 40、35 -50和81-100的肽显著抑制SEA诱导的家麝鼩呕吐,但区域161-180没有。结果表明,SEA的21-50和81-100区对SEA分子的超抗原活性和催吐活性都有重要作用,而161-180区对SEA分子的超抗原活性有重要作用,但对SEA分子的催吐活性无影响。这些区域可能是针对SEA暴露的治疗干预的重要靶点。(C)2012 Elsevier Inc. All rights reserved.
Staphylococcus aureus is a major human pathogen producing different types of toxins. Enterotoxin A (SEA) is the most common type among clinical and food-related strains. The aim of the present study was to estimate functional regions of SEA that are responsible for emetic and superantigenic activities using synthetic peptides. A series of 13 synthetic peptides corresponding to specific regions of SEA were synthesized, and the effect of these peptides on superantigenic activity of SEA including interferon gamma (IFN-gamma) production in mouse spleen cells, SEA-induced lethal shock in mice, spleen cell proliferation in house musk shrew, and emetic activity in shrews were assessed. Pre-treatment of spleen cells with synthetic peptides corresponding to the regions 21-40, 35-50, 81-100, or 161-180 of SEA significantly inhibited SEA-induced IFN-gamma production and cell proliferation. These peptides also inhibited SEA-induced lethal shock. Interestingly, peptides corresponding to regions 21-40,35-50 and 81-100 significantly inhibited SEA-induced emesis in house musk shrews, but region 161-180 did not. These findings indicated that regions 21-50 and 81-100 of SEA are important for both superantigenic and emetic activities of SEA molecule while region 161-180 is involved in superantigenic activity but not emetic activity of SEA. These regions could be important targets for therapeutic intervention against SEA exposure. (C) 2012 Elsevier Inc. All rights reserved.