Qi Linlu, Hu Mo, Fu Jiaqi, Liu Yanhua, Wu Mei, Yu Kaiwen, Liu Xiaoyun
Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, P. R. China.
Proteomics. 2017 Jul;17(13-14). doi: 10.1002/pmic.201700092. Epub 2017 Jun 23.
Systems-level analyses have the capability to offer new insight into host-pathogen interactions on the molecular level. Using Salmonella infection of host epithelial cells as a model system, we previously analyzed intracellular bacterial proteome as a window into pathogens' adaptations to their host environment [Infect. Immun. 2015; J. Proteome Res. 2017]. Herein we extended our efforts to quantitatively examine protein expression of host cells during infection. In total, we identified more than 5000 proteins with 194 differentially regulated proteins upon bacterial infection. Notably, we found marked induction of host integrin signaling and glycolytic pathways. Intriguingly, up-regulation of host glucose metabolism concurred with increased utilization of glycolysis by intracellular Salmonella during infection. In addition to immunoblotting assays, we also verified the up-regulation of PARP1 in the host nucleus by selected reaction monitoring and immunofluorescence studies. Furthermore, we provide evidence that PARP1 elevation is likely specific to Salmonella infection and independent of one of the bacterial type III secretion systems. Our work demonstrates that unbiased high-throughput proteomics can be used as a powerful approach to provide new perspectives on host-pathogen interactions.
系统层面的分析有能力在分子水平上为宿主与病原体的相互作用提供新的见解。以宿主上皮细胞的沙门氏菌感染作为一个模型系统，我们之前分析了细胞内细菌蛋白质组，将其作为了解病原体对宿主环境适应性的一个窗口[《感染与免疫》，2015年；《蛋白质组研究杂志》，2017年]。在此，我们进一步努力定量研究感染期间宿主细胞的蛋白质表达。我们总共鉴定出5000多种蛋白质，其中有194种蛋白质在细菌感染后受到差异调节。值得注意的是，我们发现宿主整合素信号传导和糖酵解途径有明显的诱导。有趣的是，宿主葡萄糖代谢的上调与感染期间细胞内沙门氏菌对糖酵解利用的增加相一致。除了免疫印迹分析外，我们还通过选择反应监测和免疫荧光研究证实了宿主细胞核中PARP1的上调。此外，我们提供证据表明PARP1的升高可能是沙门氏菌感染所特有的，并且独立于细菌的一种III型分泌系统。我们的工作表明，无偏倚的高通量蛋白质组学可以作为一种强大的方法，为宿主与病原体的相互作用提供新的视角。
