Protein Kinase LegK2 Is a Type IV Secretion System Effector Involved in Endoplasmic Reticulum Recruitment and Intracellular Replication of Legionella pneumophila
Protein Kinase LegK2 Is a Type IV Secretion System Effector Involved in Endoplasmic Reticulum Recruitment and Intracellular Replication of Legionella pneumophila
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DOI：
10.1128/iai.00805-10
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发表时间：
2011-05-01
影响因子：
3.1
通讯作者：
Doublet, Patricia
中科院分区：
文献类型：
--
作者：
Hervet, Eva;Charpentier, Xavier;Doublet, Patricia
嗜肺军团菌是军团病的病原体。这种细胞内病原体的发病机制的关键是其破坏宿主细胞防御的能力，允许在宿主细胞内的特化空泡中进行细胞内复制。Dot/Icm IV型分泌系统（T4 SS）是军团菌吞噬体改道所必需的，它能将大量细菌效应子转运到宿主细胞中。许多军团菌效应子显示出独特的真核结构域，其中包括蛋白激酶结构域。计算机分析和体外磷酸化测定鉴定了五种功能性蛋白激酶，LegK 1至LegK 5，由流行性L.嗜肺透镜应变。除LegK 5外，军团菌蛋白激酶均为T4 SS效应子。LegK 2在细菌毒力中起关键作用，如基因失活所证明的。含有空泡的legK 2突变体显示内质网标记物的招募效率较低，这导致细胞内复制延迟。考虑到legK 2的激酶死亡取代突变体表现出相同的毒力缺陷，我们在这里强调一个新的分子机制，即蛋白磷酸化，由L。pneumophila建立复制生态位和逃避宿主细胞防御。
Legionella pneumophila is the etiological agent of Legionnaires' disease. Crucial to the pathogenesis of this intracellular pathogen is its ability to subvert host cell defenses, permitting intracellular replication in specialized vacuoles within host cells. The Dot/Icm type IV secretion system (T4SS), which translocates a large number of bacterial effectors into host cell, is absolutely required for rerouting the Legionella phagosome. Many Legionella effectors display distinctive eukaryotic domains, among which are protein kinase domains. In silico analysis and in vitro phosphorylation assays identified five functional protein kinases, LegK1 to LegK5, encoded by the epidemic L. pneumophila Lens strain. Except for LegK5, the Legionella protein kinases are all T4SS effectors. LegK2 plays a key role in bacterial virulence, as demonstrated by gene inactivation. The legK2 mutant containing vacuoles displays less-efficient recruitment of endoplasmic reticulum markers, which results in delayed intracellular replication. Considering that a kinase-dead substitution mutant of legK2 exhibits the same virulence defects, we highlight here a new molecular mechanism, namely, protein phosphorylation, developed by L. pneumophila to establish a replicative niche and evade host cell defenses.