Kaufman Melissa R, Jia Jinghua, Zeng Lin, Ha Unhwan, Chow Marie, Jin Shouguang
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA1.
Department of Molecular Genetics and Microbiology, PO Box 100266, University of Florida, Gainesville, FL 32610, USA2.
Microbiology (Reading). 2000 Oct;146 ( Pt 10):2531-2541. doi: 10.1099/00221287-146-10-2531.
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 lines. 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.
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囊性纤维化患者。利用组织培养系统，发现铜绿假单胞菌的侵袭性菌株在HeLa细胞以及其他上皮和成纤维细胞系中能高频诱导细胞凋亡。感染细胞中的这种凋亡表型由几个标准确定，包括：（i）细胞形态的视觉变化；（ii）染色质浓缩和核边缘化的诱导；（iii）大量具有亚G1期DNA含量的细胞的存在；以及（iv）半胱天冬酶-3活性的激活。诱导细胞凋亡需要III型分泌机制，但不需要铜绿假单胞菌的侵袭。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突变体无法诱导细胞凋亡，用野生型exoS进行互补可恢复诱导凋亡的能力，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至关重要。
