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核糖体蛋白SA介导猪链球菌2型毒力因子烯醇化酶损伤宿主细胞线粒体
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国家自然科学基金(32072823)


Ribosomal protein mediates Streptococcus suis serotype 2 virulence factor enolase to damage host cell mitochondria
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    摘要:

    【背景】正常生理状况下核糖体蛋白SA (ribosomal protein SA, RPSA)主要在细胞内表达,参与多种细胞功能。在发生感染性疾病时,RPSA往往会异位于胞膜,介导微生物的感染。【目的】全面揭示RPSA在猪链球菌2型(Streptococcus suis serotype 2, SS2)感染宿主过程中的作用。【方法】首先利用本课题组已有的脑脊液和血清蛋白组学数据库(SS2脑膜炎感染模型的仔猪和健康仔猪),借助生物信息学手段分别筛选脑脊液和血清中的差异表达蛋白(differentially expressed proteins, DEPs),并对其涉及的信号通路进行分析。通过体外烯醇化酶(enolase, ENO)刺激宿主细胞,检测宿主细胞线粒体膜电位、钙离子含量和活性氧(reactive oxygen species, ROS)等指标变化,揭示RPSA介导SS2-ENO对宿主细胞主要能量细胞器——线粒体功能的影响。【结果】生物信息学揭示SS2感染宿主后,RPSA和相关蛋白显著富集在代谢和糖酵解/糖异生等能量有关通路。SS2-ENO刺激导致宿主细胞线粒体膜电位下降、钙离子和ROS水平升高。封闭RPSA后缓解了ENO对线粒体膜电位、细胞活性氧和细胞内钙离子含量的影响。【结论】RPSA介导SS2毒力因子ENO损伤宿主细胞线粒体功能。本研究丰富了SS2感染时RPSA的作用机制,为SS2脑膜炎疾病的防治提供了理论基础。

    Abstract:

    [Background] Under normal physiological conditions, ribosomal protein SA is mainly expressed in cells and involved in a variety of cell functions. In the occurrence of infectious diseases, RPSA expresses in the cell membrane and mediates the infection of microorganisms. [Objective] To comprehensively reveal the role of RPSA in infection of hosts by Streptococcus suis serotype 2 (SS2). [Methods] The available cerebrospinal fluid and serum proteomics database (piglets with meningitis induced by SS2 and healthy piglets) was used, and bioinformatics methods were employed to screen the differentially expressed proteins (DEPs) in cerebrospinal fluid and serum and the involved signaling pathways were summarized. The host cells were stimulated by enolase (ENO) in vitro, and the changes of mitochondrial membrane potential, Ca2+ concentration, and reactive oxygen species were detected to reveal the effect of RPSA-mediated SS2-ENO on the main functions of the energy-generating organelle mitochondria in host cells. [Results] RPSA and related proteins were mainly enriched in energy-related pathways such as metabolism and glycolysis/gluconeogenesis after SS2 infection. SS2-ENO stimulation resulted in decreased mitochondrial membrane potential and increased Ca2+ level and ROS level in host cells. Blockade of RPSA alleviated the influence of ENO on mitochondrial membrane potential, ROS and Ca2+ concentration. [Conclusion] RPSA mediates the SS2 virulence factor ENO to damage host cell mitochondria. This study enriches the mechanism of RPSA in SS2 infection and provides a theoretical basis for the prevention and treatment of SS2 meningitis.

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杜苏兰,张付贤,孙毅,刘峰,姜合祥,雷连成. 核糖体蛋白SA介导猪链球菌2型毒力因子烯醇化酶损伤宿主细胞线粒体[J]. 微生物学通报, 2023, 50(5): 2063-2075

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  • 收稿日期:2022-11-03
  • 录用日期:2022-12-15
  • 在线发布日期: 2023-05-06
  • 出版日期: 2023-05-20
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