Critical roles of amino acids Ser231, His107 and Asp156 of Staphylococcus sciuri exfoliative toxin C (ExhC) in the induction of skin exfoliations in neonate mice

Critical roles of amino acids Ser231, His107 and Asp156 of Staphylococcus sciuri exfoliative toxin C (ExhC) in the induction of skin exfoliations in neonate mice
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松鼠葡萄球菌剥脱性毒素 C (ExhC) 氨基酸 Ser231、His107 和 Asp156 在诱导新生小鼠皮肤剥脱中的关键作用

DOI:
10.2478/s11756-011-0133-z
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发表时间:
2011-10
期刊:
影响因子:
1.5
通讯作者:
Zheng, Shijun J.
Zheng, Shijun J.
中科院分区:
生物学4区
文献类型:
--
作者:
Li, Haihua;He, Fei;Zhang, Ziding;Zheng, Shijun J.

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松鼠葡萄球菌是一种罕见的人类病原体,但它可以引起广泛的人类感染。近年来,一株S.松鼠(HBXX 06)是一种携带脱落性毒素C(ExhC)的动物源性病原体,可引起仔猪的致死性渗出性表皮炎。然而,人们对这种细菌的致病性知之甚少。在这项研究中,我们预测了S。sciuri HBXX 06 ExhC,通过定点突变的方法将其活性位点的Ser 231、His 107或Asp 156替换,并以BHK-21细胞和新生小鼠为模型,检测突变ExhC的作用。有趣的是,我们发现突变体ExhC失去了对新生小鼠的剥离作用,但如果活性位点中的三个氨基酸残基中的任何一个被替换,仍然可以诱导培养细胞的坏死。这些结果表明ExhC的Ser 231、His 107和Asp 156在新生小鼠皮肤脱落的诱导中起着关键作用,这可能有助于进一步理解脱落毒素的作用机制。
Staphylococcus sciuri is a rare pathogen in humans, but it can cause a wide array of human infections. Recently a strain of S. sciuri (HBXX06) carrying exfoliative toxin C (ExhC) was reported to cause fatal exudative epidermitis in piglets and might be considered as a potential zoonotic agent. However, little is known regarding the pathogenicity of this bacterium. In this study, we predicted the three-dimensional structure of S. sciuri HBXX06 ExhC and replaced Ser231 or His107 or Asp156 in the active site of ExhC by site-directed mutagenesis, and examined the effects of mutant ExhC on BHK-21 cells and newborn mice as models. Interestingly, we found that mutant ExhC lost its exfoliative effects on newborn mice but could still induce necrosis in cultured cells if any one of the three amino acid residues in the active site was replaced. These results suggest that Ser231, His107 and Asp156 of ExhC play a critical role in the induction of skin exfoliation in neonate mice, which may help to further understand the mechanisms underlying the actions of exfoliative toxins.
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