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

兼性细胞内，专性人致病菌淋病奈瑟菌感染粘膜表面，很少引起全身感染。PorB孔蛋白在淋球菌的生存和适应中起着重要的作用，因为它已被证明可以调节宿主细胞凋亡和免疫细胞的杀菌作用。PorB能够从细菌细胞表面转运到靶细胞膜，在那里它可以快速靶向不同的细胞室，包括线粒体。PorB在结构上类似于代表真核细胞共同成分的线粒体孔蛋白。由于最近的证据表明线粒体作为凋亡细胞死亡的中心整合体起着关键作用，因此病原奈瑟菌的感染被认为是模仿祖先内共生生物与早期真核生物相互作用的方面。本应用程序的目的是研究在淋病奈瑟菌在宿主细胞中的适应PorB的作用。特别关注的是PorB的凋亡和抗凋亡功能的分子机制。进一步的方面包括从细菌到宿主细胞膜的转运机制和真核细胞内的转运。

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.