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Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways.
Journal of Microbiology ( IF 3.3 ) Pub Date : 2020-09-02 , DOI: 10.1007/s12275-020-0235-9
Xin Wang 1, 2 , Yan Li 1 , Xueping Tang 2 , Xueyi Shang 2 , Zunquan Zhao 3 , Yongqiang Jiang 3 , Yan Li 2
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Stenotrophomonas maltophilia (S. maltophilia) is a common opportunistic pathogen in intensive care units and causes infections most often after surgeries in immune-compromised patients such as those undergoing chemotherapy. Outer membrane protein A (OmpA) is the most abundant of the outer membrane proteins in S. maltophilia. Previous studies on OmpA usually focus on its interaction with the host cells and its role in vaccine development. However, the impact of OmpA on the virulence of S. maltophilia to host cells and the effects on apoptosis remain unclear. In this study, we exposed purified recombinant S. maltophilia OmpA (rOmpA) to HEp-2 cells and investigated the effects of OmpA on epithelial cell apoptosis. Morphologic and flow cytometric analyses revealed that HEp-2 cells stimulated with rOmpA multiple apoptosis features, including nuclear roundness and pyknosis, chromatin aggregation, and phosphatidylserine eversion. We found that rOmpA regulated the protein levels of Bax and Bcl-xL in HEp-2 cells, leading to changes in mitochondria permeability and the release of cytochrome c and apoptosis-inducing factors into the cytoplasm. These subsequently activate the caspase-9/caspase-3 pathway that promote apoptosis. We also observed that rOmpA enhanced the generation of reactive oxygen species and increased intracellular Ca2+ levels in HEp-2 cells. Collectively, our data suggested that rOmpA induced epithelial cells apoptosis via mi-tochondrial pathways.



中文翻译:

嗜麦芽窄食单胞菌外膜蛋白 A 通过线粒体途径诱导上皮细胞凋亡。

嗜麦芽窄食单胞菌( S. maltophilia ) 是重症监护病房中常见的机会性病原体,最常在免疫受损患者(例如接受化疗的患者)手术后引起感染。外膜蛋白 A (OmpA) 是S. maltophilia 中最丰富的外膜蛋白。以前对 OmpA 的研究通常集中在其与宿主细胞的相互作用及其在疫苗开发中的作用。然而,OmpA 对S. maltophilia对宿主细胞毒力的影响以及对细胞凋亡的影响仍不清楚。在这项研究中,我们暴露了纯化的重组S. maltophiliaOmpA (rOmpA) 作用于 HEp-2 细胞,并研究了 OmpA 对上皮细胞凋亡的影响。形态学和流式细胞仪分析表明,rOmpA 刺激 HEp-2 细胞具有多种细胞凋亡特征,包括核圆度和固缩、染色质聚集和磷脂酰丝氨酸外翻。我们发现 rOmpA 调节 HEp-2 细胞中 Bax 和 Bcl-xL 的蛋白质水平,导致线粒体通透性的变化以及细胞色素 c 和细胞凋亡诱导因子释放到细胞质中。这些随后激活促进细胞凋亡的 caspase-9/caspase-3 通路。我们还观察到 rOmpA 增强了活性氧的生成并增加了细胞内 Ca 2+HEp-2 细胞中的水平。总的来说,我们的数据表明 rOmpA 通过线粒体途径诱导上皮细胞凋亡。

更新日期:2020-09-02
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