ChpK and MazF of the toxin-antitoxin modules are involved in the virulence of Leptospira interrogans during infection (Retracted Article)
ChpK and MazF of the toxin-antitoxin modules are involved in the virulence of Leptospira interrogans during infection (Retracted Article)
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DOI：
10.1016/j.micinf.2014.10.010
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发表时间：
2015-01-01
影响因子：
5.8
通讯作者：
Yan, Jie
中科院分区：
文献类型：
--
作者：
Komi, Komi Koukoura;Ge, Yu-Mei;Yan, Jie
钩端螺旋体病是一种全球性的人畜共患传染病，致病性钩端螺旋体是其病原体。毒素抗毒素（Toxineantitoxin，TA）模块已被证实是诱导原核和真核细胞生长停滞或死亡的应激反应元件，但其在钩端螺旋体毒力中的作用尚未见报道。在这里，我们证实了所有测试的钩端螺旋体菌株具有高度保守序列的chpIK和mazEF TA模块。问号钩端螺旋体赖株chpI、chpK、迷宫和mazF基因的转录和表达在佛波酯诱导的人THP-1巨噬细胞感染过程中显著增加。在钩端螺旋体感染的THP-1细胞的细胞质部分中可检测到毒性ChpK和MazF，但未检测到抗毒性ChpI和迷宫蛋白，表明在感染期间ChpK和MazF的外分泌。转染chpK或MazF基因导致THP-1细胞活力下降和坏死，而chpI或迷宫基因转染不影响THP-1细胞的活力，但阻断了ChpK或MazF诱导的毒性。chpK或mazF基因的缺失也降低了感染后期THP-1细胞的晚期凋亡和/或坏死比率。重组蛋白MazF（rMazF）能切割钩端螺旋体和THP-1细胞的RNA，但不能切割DNA，而且这种RNA切割被rMazE阻断。然而，rChpK没有RNA或DNA降解活性。这些结果表明，TA组件中的ChpK和MazF蛋白参与了L.感染期间的疑问。(C)2014巴斯德研究所。由Elsevier Masson SAS出版。All rights reserved.
Pathogenic Leptospira species are the causative agents of leptospirosis, a global zoonotic infectious disease. Toxineantitoxin (TA) modules have been confirmed as stress-response elements that induce prokaryotic and eukaryotic cell-growth arrest or death, but their role in the virulence of Leptospira has not been reported. Here, we confirmed that all the tested leptospiral strains had the chpIK and mazEF TA modules with highly-conserved sequences. The transcription and expression of the chpI, chpK, mazE, and mazF genes of Leptospira interrogans strain Lai were significantly increased during infection of phorbol 12-myristate 13-acetate-induced human THP-1 macrophages. The toxic ChpK and MazF but not the antitoxic ChpI and MazE proteins were detectable in the cytoplasmic fraction of leptospire-infected THP-1 cells, indicating the external secretion of ChpK and MazF during infection. Transfection of the chpK or mazF gene caused decreased viability and necrosis in THP-1 cells, whereas the chpI or mazE gene transfection did not affect the viability of THP-1 cells but blocked the ChpK or MazF-induced toxicity. Deletion of the chpK or mazF gene also decreased the late-apoptotic and/or necrotic ratios of THP-1 cells at the late stages of infection. The recombinant protein MazF (rMazF) cleaved the RNAs but not the DNAs from Leptospira and THP-1 cells, and this RNA cleavage was blocked by rMazE. However, the rChpK had no RNA or DNA-degrading activity. All these findings indicate that the ChpK and MazF proteins in TA modules are involved in the virulence of L. interrogans during infection. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.