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首页> 外文期刊>Infection and immunity >The HtrA-Like Protease CD3284 Modulates Virulence of Clostridium difficile
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The HtrA-Like Protease CD3284 Modulates Virulence of Clostridium difficile

机译：HtrA样蛋白酶CD3284调节艰难梭菌的毒性。

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In the past decade, Clostridium difficile has emerged as an important gut pathogen. Symptoms of C. difficile infection range from mild diarrhea to pseudomembranous colitis. Besides the two main virulence factors toxin A and toxin B, other virulence factors are likely to play a role in the pathogenesis of the disease. In other Gram-positive and Gram-negative pathogenic bacteria, conserved high-temperature requirement A (HtrA)-like proteases have been shown to have a role in protein homeostasis and quality control. This affects the functionality of virulence factors and the resistance of bacteria to (host-induced) environmental stresses. We found that the C. difficile 630 genome encodes a single HtrA-like protease (CD3284; HtrA) and have analyzed its role in vivo and in vitro through the creation of an isogenic ClosTron-based htrA mutant of C. difficile strain 630Δerm (wild type). In contrast to the attenuated phenotype seen with htrA deletion in other pathogens, this mutant showed enhanced virulence in the Golden Syrian hamster model of acute C. difficile infection. Microarray data analysis showed a pleiotropic effect of htrA on the transcriptome of C. difficile, including upregulation of the toxin A gene. In addition, the htrA mutant showed reduced spore formation and adherence to colonic cells. Together, our data show that htrA can modulate virulence in C. difficile.
机译：在过去的十年中，艰难梭菌已成为一种重要的肠道病原体。艰难梭菌感染的症状范围从轻度腹泻到假膜性结肠炎。除了两个主要毒力因子毒素A和毒素B外，其他毒力因子也可能在疾病的发病机理中起作用。在其他革兰氏阳性和革兰氏阴性致病细菌中，保守的高温需求A（HtrA）样蛋白酶已显示出在蛋白质稳态和质量控制中的作用。这会影响毒力因子的功能以及细菌对（宿主诱导的）环境压力的抵抗力。我们发现艰难梭菌630基因组编码一个单一的HtrA样蛋白酶（CD3284; HtrA），并通过创建一个HtrA体内和体外分析了其作用。梭状芽胞杆菌630Δ erm （野生型）的基于ClosTron的 htrA 等位基因突变体。与其他病原体中 htrA 缺失的减毒表型相反，该突变体在急性艰难梭菌感染的金叙利亚仓鼠模型中显示出增强的毒力。基因芯片数据分析表明， htrA 对多毛梭菌的转录组有多效性，包括毒素A基因的上调。另外， htrA 突变体显示出减少的孢子形成和对结肠细胞的粘附。在一起，我们的数据表明 htrA 可以调节艰难梭菌的毒力。

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