Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition
Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition
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DOI：
10.1046/j.1365-2958.2003.03821.x
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Oswald, E
中科院分区：
文献类型：
--
作者：
Marchès, O;Ledger, TN;Oswald, E
肠致病性大肠杆菌（EPEC）和肠出血性大肠杆菌（EHEC）是密切相关的病原体。两者都使用由“肠细胞消失位点”（LEE）编码的III型分泌系统（TTSS），通过注射一系列效应分子来破坏并附着在上皮细胞上。在这里，我们报道了一种名为Cif的新的TTSS易位效应分子的鉴定，该分子阻断细胞周期G(2)/M转变，并通过募集局灶粘连诱导应力纤维的形成。Cif不是由LEE编码，而是由EPEC和EHEC中存在的lambdoid prophage编码。cif突变体导致微绒毛的局部消失并紧密附着在宿主细胞表面，但在阻止有丝分裂的能力上存在缺陷。当在TTSS能态lee阳性病原体中表达时，Cif被注射到被感染的上皮细胞中。这些停留在G(2)/M期的细胞显示出无活性磷酸化Cdk1的积累。总之，Cif是一个不断增长的细菌环调节蛋白家族的新成员，它破坏宿主真核细胞周期。
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are closely related pathogens. Both use a type III secretion system (TTSS) encoded by the 'locus of enterocyte effacement' (LEE) to subvert and attach to epithelial cells through the injection of a repertoire of effector molecules. Here, we report the identification of a new TTSS translocated effector molecule called Cif, which blocks cell cycle G(2)/M transition and induces the formation of stress fibres through the recruitment of focal adhesions. Cif is not encoded by the LEE but by a lambdoid prophage present in EPEC and EHEC. A cif mutant causes localized effacement of microvilli and intimately attaches to the host cell surface, but is defective in the ability to block mitosis. When expressed in TTSS competent LEE-positive pathogens, Cif is injected into the infected epithelial cells. These cells arrested at the G(2)/M phase displayed accumulation of inactive phosphorylated Cdk1. In conclusion, Cif is a new member of a growing family of bacterial cyclomodulins that subvert the host eukaryotic cell cycle.