Evidence for holin function of tcdE gene in the pathogenicity of Clostridium difficile

Evidence for holin function of tcdE gene in the pathogenicity of Clostridium difficile
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DOI:
10.1099/0022-1317-50-7-613
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发表时间:
2001-07-01
影响因子:
3
通讯作者:
Song, KP
Song, KP
中科院分区:
医学3区
文献类型:
--
作者:
Tan, KS;Wee, BY;Song, KP

文献摘要

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艰难梭菌产生两种大的细菌毒素,分别称为毒素A(TcdA)和毒素B(TcdB),TcdA和TcdB基因位于艰难梭菌的致病基因座上,这是艰难梭菌特有的致病基因。这两个毒素基因之间存在tcdE,这是一个功能未知的501个碱基的小开放阅读框。TcdE基因在大肠杆菌中的表达导致细菌细胞死亡。对TcdE氨基酸序列的计算分析揭示了TcdE的结构特征,它与一类名为Holins的噬菌体蛋白非常相似,Holins是引起细菌宿主裂解影响后代噬菌体释放的细胞溶解蛋白,通过对TcdE重组表达产物的透射电子显微镜进一步分析,证实TcdE的作用部位在细菌细胞膜上。这些结果表明,TcdE在结构和功能上与Holin蛋白相似,TcdE可能是一种裂解蛋白,促进TcdA和TcdB释放到细胞外环境,因为这些毒素缺乏信号肽。
Toxigenic strains of Clostridium difficile produce two large bacterial toxins called toxins A (TcdA) and B (TcdB), tcdA and tcdB genes are located on the pathogenicity locus of C, difficile, a unique characteristic of toxigenic strains of this species. Intergenic to the two toxin genes is tcdE, a small 501-bp open reading frame of unknown function. Expression of the tcdE gene in Escherichia coli caused bacterial cell death. Computational analysis of the amino acid sequence of TcdE revealed structural features that are strikingly similar to a class of bacteriophage proteins called holins, Holins are cytolytic proteins that cause lysis of bacterial hosts to effect the release of progeny phages, Further analysis of the recombinant done expressing TcdE by transmission electron microscopy confirmed that the site of action of TcdE is on the bacterial cell membrane. The results provide evidence that TcdE is structurally and functionally similar to holin proteins, TcdE may function as a lytic protein to facilitate the release of TcdA and TcdB to the extracellular environment, as these toxins lack signal peptide.