RD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion
RD1 region in mycobacterial genome is involved in the induction of necrosis in infected RAW264 cells via mitochondrial membrane damage and ATP depletion
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DOI：
10.1111/j.1574-6968.2007.00838.x
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发表时间：
2007-09-01
影响因子：
2.1
通讯作者：
Mitsuyama, Masao
中科院分区：
文献类型：
--
作者：
Kaku, Taijin;Kawamura, Ikuo;Mitsuyama, Masao
结果表明，强毒力结核分枝杆菌 H37Rv 在感染后 24 小时诱导受感染 RAW264 细胞坏死，而无毒力 H37Ra 和缺乏 RD1 区域的减毒 H37Rv 突变体 (H37Rv Delta RD1) 导致受感染细胞坏死较少。虽然 H37Rv 导致线粒体内膜损伤并降低细胞内 ATP 水平，但 H37Rv Delta RD1 在受感染的细胞中并未表现出这些有害作用。另一方面，H37Rv或H37Rv Delta RD1感染后细胞内活性氧水平没有差异，并且H37Rv Delta RD1和H37Ra的细胞内细菌数量与H37Rv相当。这些结果表明，H37Rv 的一些毒力因子可能通过诱导线粒体功能障碍和细胞内 ATP 耗竭而导致受感染细胞坏死。 RD1似乎编码一些可能在结核分枝杆菌感染后诱导宿主细胞坏死中发挥核心作用的成分。
It was shown that virulent Mycobacterium tuberculosis H37Rv induces necrosis of infected RAW264 cells at 24 h post infection while avirulent H37Ra and an attenuated H37Rv mutant that is deficient for RD1 region (H37Rv Delta RD1) cause less necrosis of the infected cells. While H37Rv caused damage of the mitochondrial inner membrane and decreased the level of intracellular ATP, H37Rv Delta RD1 did not exhibit these harmful effects in infected cells. On the other hand, there was no difference in the level of intracellular reactive oxygen species after infection with H37Rv or H37Rv Delta RD1, and the intracellular bacterial numbers of H37Rv Delta RD1 and H37Ra were comparable to that of H37Rv. These results suggested that some virulence factors of H37Rv may contribute to the necrosis of infected cells through induction of mitochondrial dysfunction and depletion of intracellular ATP. RD1 appeared to encode some components possibly playing a central role in the induction of host cell necrosis after M. tuberculosis infection.