Haemophilus parasuis cytolethal distending toxin induces cell cycle arrest and p53-dependent apoptosis.
Haemophilus parasuis cytolethal distending toxin induces cell cycle arrest and p53-dependent apoptosis.
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DOI：
10.1371/journal.pone.0177199
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Li G;Niu H;Zhang Y;Li Y;Xie F;Langford PR;Liu S;Wang C
副猪嗜血杆菌是猪格拉瑟病的病原体。细胞致死膨胀毒素（CDT）是副猪嗜血菌的重要毒力因子。它由三个亚基组成：CdtA、CdtB 和 CdtC，当信号肽被去除后，所有亚基都在大肠杆菌中以可溶形式成功表达。纯化的 CdtB 具有 DNase 活性，即在细胞停滞和凋亡之前在体外和体内引起 DNA 双链损伤。流式细胞术分析表明，单独的 CdtB 可以诱导 PK-15 猪肾和肺泡巨噬细胞 (PAM) 细胞的细胞周期停滞和凋亡，并且 CdtA 或/和 CdtC 可以增强这种作用。 CDT 全毒素可导致 PK-15 和 PAM 细胞显着细胞膨胀、G2 期停滞和凋亡。 CDT全毒素诱导的细胞凋亡被pifithrin-α显着抑制，这表明它是p53依赖性的。结果表明副猪嗜血菌 CDT 全毒素是主要毒力因子。
Haemophilus parasuis is the causative agent of Glasser’s disease in pigs. Cytolethal distending toxin (CDT) is an important virulence factor of H. parasuis. It is composed of three subunits: CdtA, CdtB and CdtC and all were successfully expressed in soluble form in Escherichia coli when the signal peptides were removed. Purified CdtB had DNase activity, i.e. caused DNA double strand damage, in vitro and in vivo prior to cell arrest and apoptosis. Flow cytometry analysis showed CdtB alone could induce cell cycle arrest and apoptosis in PK-15 porcine kidney and pulmonary alveolar macrophage (PAM) cells, which could be enhanced by CdtA or/and CdtC. CDT holotoxin could lead to significant cell distension, G2 arrest and apoptotic death in PK-15 and PAM cells. The apoptosis induced by CDT holotoxin was significantly inhibited by pifithrin-α, which indicates that it is p53-dependent. The results suggest that H. parasuis CDT holotoxin is a major virulence factor.