Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS
Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS
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DOI：
10.1099/00221287-146-10-2531
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发表时间：
2000-10-01
期刊：
影响因子：
--
通讯作者：
Jin, SG
中科院分区：
文献类型：
--
作者：
Kaufman, MR;Jia, JH;Jin, SG
铜绿假单胞菌是一种机会致病菌，主要感染免疫功能低下的个体和囊性纤维化患者。使用组织培养系统，发现铜绿假单胞菌的侵袭性菌株在HeLa和其他上皮和成纤维细胞西内斯中以高频率诱导细胞凋亡。通过几个标准确定感染细胞中的这种凋亡表型，包括（i）细胞形态的视觉变化，（ii）诱导染色质凝聚和核边缘化，（iii）存在高百分比的具有subG 1 DNA含量的细胞，和（iv）半胱天冬酶-3活性的活化。诱导凋亡需要诱导III型分泌机制，而不是铜绿假单胞菌的侵入。细胞凋亡表型与感染后早期宿主细胞中发生的细胞骨架重排无关。铜绿假单胞菌exoS的突变体不能诱导细胞凋亡，与野生型exoS的互补恢复了细胞凋亡诱导能力，表明ExoS是效应分子。对exoS活性突变体的分析表明，ExoS的ADP-核糖基化能力对于诱导凋亡途径是必不可少的。
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that primarily infects immunocompromised individuals and patients with cystic fibrosis. Using a tissue culture system, invasive strains of P. aeruginosa were discovered to induce apoptosis at high frequency in HeLa and other epithelial and fibroblast cell sines. This apoptotic phenotype in the infected cells was determined by several criteria including (i) visual changes in cell morphology, (ii) induction of chromatin condensation and nuclear marginalization, (iii) the presence of a high percentage of cells with subG1 DNA content, and (iv) activation of caspase-3 activity. Induction of the type III secretion machinery, but not invasion of P. aeruginosa is required for induction of apoptosis. The apoptosis phenotype is independent of the cytoskeletal rearrangements that occur in the host cell early after infection. Mutants in P. aeruginosa exoS fail to induce apoptosis and complementation with wild-type exoS restored the apoptosis-inducing capacity, demonstrating that ExoS is the effector molecule. Analysis of exoS activity mutants shows that the ADP-ribosylating capacity of ExoS is essential for inducing the apoptotic pathway.