The mechanism of killing and exiting the protozoan host Acanthamoeba polyphaga by Legionella pneumophila
The mechanism of killing and exiting the protozoan host Acanthamoeba polyphaga by Legionella pneumophila
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DOI：
10.1046/j.1462-2920.2000.00076.x
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发表时间：
2000-02-01
影响因子：
5.1
通讯作者：
Abu Kwaik, Y
中科院分区：
文献类型：
--
作者：
Gao, LY;Abu Kwaik, Y
嗜肺军团菌引起军团病的能力取决于其在肺泡腔细胞内复制的能力。细菌在两个阶段杀死哺乳动物细胞：在感染的早期阶段诱导细胞凋亡，随后在感染的后期阶段由成孔活性介导的独立且快速的坏死。在环境中，L。嗜肺虫是原生动物的寄生虫。L.嗜肺菌在利用原生动物细胞进行细胞内增殖后杀死原生动物细胞的情况尚不清楚。在努力破译这些机制，我们已经研究了诱导细胞凋亡和坏死的原生动物多食阿米巴感染L。pneumophila，我们的数据表明，虽然A.在放线菌素D、L处理后，polyphaga经历凋亡。嗜肺菌不诱导这些细胞的凋亡。相反，胞内L. pneumophila诱导A. polyphaga，这是介导的孔形成活动。L.突变体孔形成活性表达缺陷的嗜肺菌在A.亲本菌株细菌引起所有A.在感染后48 h内，所有的细胞内细菌都被释放到组织培养基中。相反，所有被突变体感染的细胞保持完整，细胞内的细菌被“困”在A。多食虫细胞内复制终止后。胞内复制终止后未能退出宿主细胞会导致A内突变菌株细菌的活力逐渐下降。感染后48 h开始出现多食性。结果表明，L。pneumophila不是A.在细胞内复制终止时，它是杀死和离开原生动物宿主所必需的。
The ability of Legionella pneumophila to cause legionnaires' disease is dependent on its capacity to replicate within cells in the alveolar spaces. The bacteria kill mammalian cells in two phases: induction of apoptosis during the early stages of infection, followed by an independent and rapid necrosis during later stages of the infection, mediated by a pore-forming activity. In the environment, L. pneumophila is a parasite of protozoa. The molecular mechanisms by which L. pneumophila kills the protozoan cells, after their exploitation for intracellular proliferation, are not known. In an effort to decipher these mechanisms, we have examined induction of both apoptosis and necrosis in the protozoan Acanthamoeba polyphaga upon infection by L. pneumophila, Our data show that, although A. polyphaga undergoes apoptosis following treatment with actinomycin D, L. pneumophila does not induce apoptosis in these cells. Instead, intracellular L. pneumophila induces necrotic death in A. polyphaga, which is mediated by the pore-forming activity. Mutants of L. pneumophila defective in expression of the pore-forming activity are indistinguishable from the parental strain in intracellular replication within A. polyphaga, The parental strain bacteria cause necrosis-mediated lysis of all the A. polyphaga cells within 48 h after infection, and all the intracellular bacteria are released into the tissue culture medium. In contrast, all cells infected by the mutants remain intact, and the intracellular bacteria are 'trapped' within A. polyphaga after the termination of intracellular replication. Failure to exit the host cell after termination of intracellular replication results in a gradual decline in the viability of the mutant strain bacteria within A. polyphaga starting 48 h after infection. Our data show that the pore-forming activity of L. pneumophila is not required for intracellular bacterial replication within A. polyphaga but is required for killing and exiting the protozoan host upon termination of intracellular replication.