Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Cell Microbiol. 2017 Dec;19(12). doi: 10.1111/cmi.12771. Epub 2017 Aug 25.
Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.
外膜炎症蛋白 A（OipA）是与胃癌和溃疡发展相关的重要毒力因子；然而，其结果尚未得到很好的确立，且结果颇具争议。本研究旨在利用携带 oipA“开”和“关”启动子的临床菌株阐明 OipA 在幽门螺杆菌感染中的作用。采用液相色谱/质谱对 AGS 细胞进行 OipA“开”和“关”菌株预感染和感染后的蛋白质组学分析。进行 AGS 细胞凋亡和细胞周期检测。此外，通过 Western blot 筛选空泡细胞毒素 A（VacA）的表达。与 OipA“开”菌株相比，感染 OipA“关”菌株后AGS 细胞中先前被认为与胃疾病有关或发挥作用的蛋白表达下调。此外，与 OipA“开”菌株相比，oipA“关”和ΔoipA 引起 AGS 细胞凋亡和 G0/G1 细胞周期阻滞的水平更高。有趣的是，缺失 oipA 会增加细菌 VacA 的产生。在没有 OipA 的情况下，H. pylori 诱导细胞凋亡和抑制与人类疾病相关蛋白表达的能力表明，与表达 OipA 的菌株相比，不表达 OipA 的菌株的毒力可能较低，甚至可能对致癌作用具有保护作用。这可能解释了东亚地区胃癌发病率较高的原因，东亚地区以 oipA“开”菌株为主。
