Induction of apoptosis by the PorB porin of Neisseria gonorrhoeae: A paradigm for the evolution of programmed cell death

淋病奈瑟菌 PorB 孔蛋白诱导细胞凋亡：程序性细胞死亡进化的范例

• 批准号: 5373295
• 负责人: Professor Dr. Thomas Rudel
• 金额: --
• 依托单位: Lehrstuhl für Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5373295?language=en
• 关键词: Induction; apoptosis; PorB; porin; Neisseria

The facultative intracellular, obligate human pathogenic bacterium Neisseria gonorrhoeae infects mucosal surfaces and rarely causes systemic infections. The PorB porin plays an important role for the survival and adaptation of gonococci since it has been shown to modulate host cell apoptosis and the bactericidal action of immune cells. PorB is capable of translocating from the bacterial cell surface into target cell membranes where it is rapidly targeted to different cellular compartments including the mitochondria. PorB structurally resembles the mitochondrial porins representing common constituents of eukaryotic cells. Since recent evidences assume a critical role of mitochondria as central integrators of apoptotic cell death, the infection with pathogenic Neisseria species is considered to mimic aspects of the interaction of ancestral endosymbionts with early eukaryotic organisms. The goal of this application is to investigate on the role of PorB for the adaptation of N. gonorrhoeae in host cells. A special focus will be the molecular mechanisms of the apoptotic and anti-apoptotic function of PorB. Further aspects cover the mechanism of PorB translocation from the bacteria into host cell membranes and the transport of PorB inside eukaryotic cells.

兼性细胞内专性人类病原性细菌淋病奈瑟氏菌感染粘膜表面，很少引起全身感染。PorB孔蛋白对淋球菌的生存和适应起着重要作用，因为它已被证明可以调节宿主细胞的凋亡和免疫细胞的杀菌作用。PorB能够从细菌细胞表面转移到靶细胞膜中，在那里它被快速靶向到不同的细胞区室，包括线粒体。PorB在结构上类似于代表真核细胞的常见组分的线粒体孔蛋白。由于最近的证据假设线粒体作为细胞凋亡的中心整合者发挥着关键作用，因此致病性奈瑟氏菌物种的感染被认为模拟了祖先内共生菌与早期真核生物相互作用的方面。本申请的目的是研究PorB在N.淋病在宿主细胞中。一个特别的焦点将是凋亡和抗凋亡功能的PorB的分子机制。其他方面包括PorB从细菌易位到宿主细胞膜的机制和PorB在真核细胞内的转运。