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首页> 外文期刊>Infection and immunity >Expression of Pseudomonas aeruginosa Toxin ExoS Effectively Induces Apoptosis in Host Cells
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Expression of Pseudomonas aeruginosa Toxin ExoS Effectively Induces Apoptosis in Host Cells

机译：铜绿假单胞菌毒素ExoS的表达有效诱导宿主细胞凋亡。

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Pseudomonas aeruginosa is an opportunistic bacterial pathogen that primarily infects immunocompromised individuals and patients with cystic fibrosis. Invasive strains of P. aeruginosa are known to induce apoptosis at a high frequency in HeLa cells and in many other cell lines, a process that is dependent on the ADP-ribosylation (ADPRT) activity of a type III secreted protein ExoS. In our previous report, it was proposed that P. aeruginosa secreting ExoS, upon infection, shuts down host cell survival signal pathways by inhibiting ERK1/2 and p38 activation, and it activates proapoptotic pathways through activation of JNK1/2, leading ultimately to cytochrome c release and activation of caspases. In this study, we demonstrate that the expression of ExoS in HeLa cells by eukaryotic expression vector effectively caused apoptosis in an ADPRT activity-dependent manner, indicating that ExoS alone is sufficient to trigger apoptotic death of host cells independent of any other bacterial factors. By expressing an EGFP-ExoS fusion protein, we were able to directly correlate the death of HeLa cells with the presence of intracellular ExoS and further proved the dependence of this process on both JNK activation and mitochondrial proapoptotic event. The cellular pathway responsible for the ExoS-induced cytotoxicity appears to be well conserved, since the expression of the ADPRT-competent ExoS also induced rapid cell death in the Drosophila melanogaster S2 cell lines. The presented study not only highlights the ability of ExoS ADPRT to modulate host cell signaling, eventually leading to apoptosis, but also establishes ExoS as a valuable tool, in principle, for the elucidation of apoptosis mechanisms.
机译：铜绿假单胞菌是一种机会性细菌病原体，主要感染免疫功能低下的个体和患有囊性纤维化的患者。 P的入侵株。已知铜绿假单胞菌可在HeLa细胞和许多其他细胞系中以高频率诱导细胞凋亡，这一过程取决于III型分泌蛋白ExoS的ADP-核糖基化（ADPRT）活性。在我们以前的报告中，建议使用 P。感染时分泌铜绿的ExoS通过抑制ERK1 / 2和p38激活而关闭宿主细胞存活信号通路，并通过激活JNK1 / 2激活促凋亡途径，最终导致细胞色素 c 释放和激活胱天蛋白酶。在这项研究中，我们证明了真核表达载体在HeLa细胞中表达ExoS以ADPRT活性依赖性方式有效引起了细胞凋亡，表明单独的ExoS足以引发宿主细胞凋亡性死亡，而与其他细菌因素无关。通过表达EGFP-ExoS融合蛋白，我们能够将HeLa细胞的死亡与细胞内ExoS的存在直接相关，并进一步证明了该过程对JNK激活和线粒体促凋亡事件的依赖性。负责ExoS诱导的细胞毒性的细胞途径似乎是非常保守的，因为具有ADPRT能力的ExoS的表达还诱导了果蝇S2细胞系中的快速细胞死亡。提出的研究不仅强调了ExoS ADPRT调节宿主细胞信号转导并最终导致细胞凋亡的能力，而且从原理上讲，还建立了ExoS作为有价值的工具，可用于阐明细胞凋亡机制。

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