Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread
Differential function of Listeria monocytogenes listeriolysin O and phospholipases C in vacuolar dissolution following cell-to-cell spread
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DOI：
10.1111/j.1462-5822.2006.00780.x
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Higgins, Darren E.
中科院分区：
文献类型：
--
作者：
Alberti-Segui, Christine;Goeden, Kathryn R.;Higgins, Darren E.
我们研究了溶血素O（LLO）和细菌磷脂酶PI-PLC和PC-PLC在单核细胞增生李斯特菌细胞间传播中的作用。我们发现LLO对于原代小鼠巨噬细胞中的细胞间扩散是必不可少的。电子显微照片显示，在没有持续LLO表达的情况下，细菌仍然被困在具有双膜或单膜的次级扩展空泡中。在缺乏PI-PLC和PC-PLC的细菌中，感染开始后停止LLO表达导致双膜隔室中捕获的细菌比例显著增加。我们认为细菌磷脂酶参与了扩展液泡内膜的溶解，但不足以破坏外膜。因此，我们将LLO确定为外膜破坏的关键因素。该模型与以下观察结果一致，即LLO对于从人巨噬细胞到其中LLO对于空泡逃逸不需要的细胞类型的细胞间扩散是不可接受的。这些数据表明，在人类感染L。因此，即使在LLO表达不存在的情况下，单核细胞增多症向远处器官的转移也可能发生，并且细菌磷脂酶可能足以介导持续的细胞间扩散。
We investigated the role of listeriolysin O (LLO) and the bacterial phospholipases PI-PLC and PC-PLC in cell-to-cell spread of Listeria monocytogenes. We showed that LLO is essential for cell-to-cell spread in primary murine macrophages. Electron micrographs revealed that in the absence of continued LLO expression, bacteria remain trapped in secondary spreading vacuoles having either a double or single membrane. In bacteria lacking PI-PLC and PC-PLC, cessation of LLO expression after initiation of infection resulted in a significant increase in the proportion of bacteria trapped in double-membrane compartments. We propose that the bacterial phospholipases are involved in the dissolution of the inner membrane of the spreading vacuole, yet are not sufficient for disruption of the outer membrane. As a consequence, we identified LLO as a key factor in the disruption of the outer membrane. This model is consistent with the observation that LLO is dispensable for cell-to-cell spread from human macrophages into a cell type in which LLO is not required for vacuolar escape. These data suggest that during human infection, spreading of L. monocytogenes to distant organs is likely to occur even in the absence of LLO expression, and that the bacterial phospholipases may be sufficient to mediate continued cell-to-cell spread.