Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth
Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth
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DOI：
10.1046/j.1365-2958.2000.02176.x
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发表时间：
2000-11-01
影响因子：
3.6
通讯作者：
Roy, CR
中科院分区：
文献类型：
--
作者：
Coers, J;Kagan, JC;Roy, CR
嗜肺军团菌是一种细菌病原体，可以进入人类肺部并在肺泡巨噬细胞内生长。为了在吞噬宿主细胞内生长，细菌必须产生一种特殊的细胞器来限制与溶酶体的融合，这种复制细胞器的生物发生由 24 点和 icm 基因控制，这些基因编码 iv 型相关的运输装置。为了了解这种转运蛋白的功能，对同基因嗜肺军团菌 dot 和 icm 突变体进行了表征，并鉴定了三种不同的表型类别。我们的数据表明，除了编码核心 Dot/Icm 转运装置的基因之外，孔的形成和吞噬体运输的调节还需要基因子集。为了在分子水平上了解毒力所需的活性，我们研究了蛋白质-蛋白质相互作用，通过酵母双杂交和凝胶叠加分析检测了不同 Icm 蛋白质之间的特异性相互作用。这些数据支持一个模型，其中 IcmQ-IcmR 复合物调节将蛋白质递送到宿主细胞中的易位通道的形成，并且 IcmS-IcmW 复合物对于输出调节吞噬体运输的毒力决定簇是必需的。
Legionella pneumophila is a bacterial pathogen that can enter the human lung and grow inside alveolar macrophages, To grow within phagocytic host cells, the bacteria must create a specialized organelle that restricts fusion with lysosomes, Biogenesis of this replicative organelle is controlled by 24 dot and icm genes, which encode a type iv-related transport apparatus. To understand how this transporter functions, isogenic L. pneumophila dot and icm mutants were characterized, and three distinct phenotypic categories were identified. Our data show that, in addition to genes that encode the core Dot/Icm transport apparatus, subsets of genes are required for pore formation and modulation of phagosome trafficking. To understand activities required for virulence at a molecular level, we investigated protein-protein interactions, Specific interactions between different Icm proteins were detected by yeast two-hybrid and gel overlay analysis. These data support a model in which the IcmQ-IcmR complex regulates the formation of a translocation channel that delivers proteins into host cells, and the IcmS-IcmW complex is required for export of virulence determinants that modulate phagosome trafficking.