Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
Peptides. 2012 Nov;38(1):1-7. doi: 10.1016/j.peptides.2012.08.013. Epub 2012 Aug 28.
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 γ (IFN-γ) 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-γ 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.
金黄色葡萄球菌是一种主要的人类病原体,能产生不同类型的毒素。肠毒素 A(SEA)是临床和与食物相关的菌株中最常见的类型。本研究旨在使用合成肽来估计SEA 的致呕和超抗原活性负责的功能区域。合成了一系列 13 种对应于 SEA 特定区域的合成肽,并评估了这些肽对 SEA 的超抗原活性的影响,包括干扰素 γ(IFN-γ)在小鼠脾细胞中的产生、SEA 在小鼠中引起的致死性休克、在屋麝鼩中的脾细胞增殖以及在麝鼩中的致呕活性。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,可显著抑制 SEA 诱导的 IFN-γ产生和细胞增殖。这些肽也抑制了 SEA 诱导的致死性休克。有趣的是,对应于 SEA 的区域 21-40、35-50 和 81-100 的肽显著抑制了屋麝鼩中 SEA 诱导的呕吐,但区域 161-180 则没有。这些发现表明 SEA 的区域 21-50 和 81-100 对 SEA 分子的超抗原和致呕活性都很重要,而区域 161-180 则参与了 SEA 的超抗原活性,但不参与致呕活性。这些区域可能是针对 SEA 暴露进行治疗干预的重要靶点。