Transcriptional down-regulation and rRNA cleavage in Dictyostelium discoideum mitochondria during Legionella pneumophila infection.
Transcriptional down-regulation and rRNA cleavage in Dictyostelium discoideum mitochondria during Legionella pneumophila infection.
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嗜肺军团菌感染期间盘基网柄菌线粒体中的转录下调和 rRNA 裂解。
DOI：
10.1371/journal.pone.0005706
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发表时间：
2009-05-27
期刊：
影响因子：
3.7
通讯作者：
Kuspa A
中科院分区：
文献类型：
--
作者：
Zhang C;Kuspa A
细菌病原体在侵入真核细胞时采用多种生存策略。盘基网柄菌变形虫被用作模型宿主，以研究军团病病原体嗜肺军团菌杀死真核细胞的致病机制。在这里，我们发现嗜肺军团菌感染盘状 D. 会导致线粒体信使 RNA 减少，这种情况在可检测到的宿主细胞死亡之前 8 小时以上就开始减少。这些变化可以通过过氧化氢治疗来模拟，但不能通过其他细胞毒性药物来模拟。在感染过程中，线粒体大亚基核糖体 RNA (LSU rRNA) 也在三个特定位点被切割。首先出现两个 LSU rRNA 片段，然后是由额外切割事件产生的较小片段。最初的 LSU rRNA 切割位点预计位于线粒体核糖体大亚基的表面，而两个次级位点映射到与小亚基的预测界面。将盘状 D. 暴露于过氧化氢或其他以多种方式杀死细胞的细胞毒性化学物质后，没有观察到 LSU rRNA 裂解。裂解需要有功能的嗜肺军团菌 II 型和 IV 型分泌系统，从而建立了嗜肺军团菌和盘状嗜肺军团菌 LSU rRNA 破坏的发病机制之间的相关性。在卡氏棘阿米巴或人 U937 细胞的嗜肺军团菌感染中未观察到 LSU rRNA 裂解，表明嗜肺军团菌使用不同的机制来中断不同宿主的代谢。因此，嗜肺军团菌感染盘状 D. 会导致线粒体 RNA 的急剧减少，并导致线粒体 rRNA 的特异性裂解。线粒体核糖体上切割位点的预测位置表明 rRNA 破坏是由特定的事件序列启动的。这些发现表明，嗜肺军团菌在感染过程中会特异性破坏盘状线虫中的线粒体蛋白质合成。
Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells. Here we show that the infection of D. discoideum by L. pneumophila results in a decrease in mitochondrial messenger RNAs, beginning more than 8 hours prior to detectable host cell death. These changes can be mimicked by hydrogen peroxide treatment, but not by other cytotoxic agents. The mitochondrial large subunit ribosomal RNA (LSU rRNA) is also cleaved at three specific sites during the course of infection. Two LSU rRNA fragments appear first, followed by smaller fragments produced by additional cleavage events. The initial LSU rRNA cleavage site is predicted to be on the surface of the large subunit of the mitochondrial ribosome, while two secondary sites map to the predicted interface with the small subunit. No LSU rRNA cleavage was observed after exposure of D. discoideum to hydrogen peroxide, or other cytotoxic chemicals that kill cells in a variety of ways. Functional L. pneumophila type II and type IV secretion systems are required for the cleavage, establishing a correlation between the pathogenesis of L. pneumophila and D. discoideum LSU rRNA destruction. LSU rRNA cleavage was not observed in L. pneumophila infections of Acanthamoeba castellanii or human U937 cells, suggesting that L. pneumophila uses distinct mechanisms to interrupt metabolism in different hosts. Thus, L. pneumophila infection of D. discoideum results in dramatic decrease of mitochondrial RNAs, and in the specific cleavage of mitochondrial rRNA. The predicted location of the cleavage sites on the mitochondrial ribosome suggests that rRNA destruction is initiated by a specific sequence of events. These findings suggest that L. pneumophila specifically disrupts mitochondrial protein synthesis in D. discoideum during the course of infection.
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影响因子：
64.8
作者：
Ban, N;Nissen, P;Steitz, TA
通讯作者：
Steitz, TA
DOI：
10.1073/pnas.85.23.8998
发表时间：
1988-12-01
影响因子：
11.1
作者：
FROHMAN, MA;DUSH, MK;MARTIN, GR
通讯作者：
MARTIN, GR
影响因子：
3.4
作者：
Farbrother, P;Wagner, C;Eichinger, L
通讯作者：
Eichinger, L
影响因子：
3.1
作者：
Byrne, B;Swanson, MS
通讯作者：
Swanson, MS
影响因子：
3.1
作者：
Hales, LM;Shuman, HA
通讯作者：
Shuman, HA