SPP 2225: Exit strategies of intracellular pathogens

SPP 2225是一个由微生物学家和感染研究人员组成的跨学科联盟，旨在探索细胞内细菌、寄生虫和真菌病原体退出包膜宿主细胞的一系列策略。宿主细胞的退出遵循宿主-病原体共同进化过程中进化出来的一个积极协调的程序，并依赖于宿主细胞和微生物因素之间的动态相互作用。在不同的细胞内病原体群体中，至少有三种不同的宿主细胞退出途径已经趋同进化，(1)启动程序性细胞死亡，(2)宿主细胞的活性裂解破坏，以及(3)不进行宿主细胞裂解的膜依赖性退出。SPP 2225的目标是剖析触发、调节和同步病原体退出的分子机制，发现宿主细胞退出的顺序步骤以及退出途径与宿主细胞特异性之间的联系。SPP 2225项目中所代表的病原体的广度允许比较策略，找到相似之处并得出宿主细胞退出的普遍机制的结论，以及确定退出途径的物种或组织特异性变化。在SPP 2225的第二个资助期，我们将应用迄今收集的数据，以及在第一个资助期开发的分子技术和遗传工具，扩大我们对宿主细胞退出机制的知识，并揭示退出策略与疾病进展之间的联系。通过SPP 2225获得的知识不仅将加深对人类病原体感染的基本过程的了解，而且将进一步推进我们对组织炎症和感染诱导的器官功能障碍的理解。SPP 2225获得的结果最终将导致确定新的干预目标，以对抗世界范围内的人类传染病，鉴于微生物对当前治疗方案的耐药性日益增加，这一点尤为重要。实施了各种协调措施，以实现SPP 2225联盟科学家之间的联网，加强SPP 2225的知名度，并促进对早期职业研究人员的培训。战略概念包括讲习班和专题讨论会以及两个技术平台，此外还有网络和启动基金、性别平等以及公共关系措施。

The priority programme SPP 2225 is an interdisciplinary consortium of microbiologists and infection researchers exploring the spectrum of strategies that are employed by intracellular bacterial, parasitic and fungal pathogens to exit the enveloping host cell. Host cell exit follows an actively orchestrated programme that has evolved during host-pathogen co-evolution and relies on the dynamic interplay between host cell and microbial factors. At least three distinct pathways of host cell exit have convergently evolved among the diverse groups of intracellular pathogens, (1) initiation of programmed cell death, (2) active lytic destruction of the host cell, and (3) membrane-dependent exit without host cell lysis. It is the goal of SPP 2225 to dissect the molecular mechanisms that trigger, regulate, and synchronize pathogen exit and to discover the sequential steps of host cell exit as well as the link between exit pathway and host cell specificity. The breadth of pathogens represented in the SPP 2225 projects allows to compare strategies, find parallels and draw conclusions on universal mechanisms of host cell exit as well as to identify species- or tissue-specific variations of exit pathways. In the second funding period of the SPP 2225, we will apply the data collected so far, as well as the molecular techniques and genetic tools that have been developed during the first funding period, to expand our know-how of the host cell exit mechanisms and to unveil the link between exit strategy and disease progression. Knowledge gained by SPP 2225 will not only deepen insights into the fundamental processes of infection by human pathogens, but will additionally advance our understanding of tissue inflammation and infection-induced organ dysfunction. Results obtained by the SPP 2225 will eventually lead to the identification of novel interventional targets to combat human infectious diseases worldwide, which is especially important in view of the increasing microbial resistance to current treatment regimes. Various coordination measures have been implemented to enable networking among the scientists of the SPP 2225 consortium, to strengthen the visibility of the SPP 2225 and to promote the training of early career researchers. The strategic concept includes workshops and symposia as well as two technical platforms in addition to network and start-up funds and gender equality as well as public relation measures.