Deciphering the role of spingolipids in bacterial egress

用胞内病原体感染真核宿主细胞是一个协调良好的过程。它包括宿主细胞的粘附和侵入，建立一个复制允许的细胞内生态位和从感染细胞释放感染性后代。除了研究充分的过程入侵和细胞内存活，从宿主细胞的出口是感染过程中的关键步骤，迄今尚未深入研究。病原体可以通过不同的途径离开宿主细胞，包括宿主细胞的裂解或通过导致病原体流出而不导致宿主细胞死亡的非裂解过程。衣原体属的挤出形成是后一种的一个例子。目前尚不清楚退出途径是如何调节的，以及在某些条件下哪些因素会触发不同的退出策略。特别是，鞘脂作为生物活性脂质调节细胞途径（包括信号传导和分泌）的作用尚未在非裂解性细菌排出的背景下得到解决。我的小组的初步数据表明鞘脂控制衣原体的挤出形成。在这项提案中，我们的目标是通过研究鞘脂在调节人畜共患病原体C的挤出形成中的新作用来填补这一知识空白。鹦鹉热作为模式生物通过控制信号传导途径、膜动力学和/或细菌蛋白的表达和定位。此外，还将研究鞘脂对其他病原体退出策略的影响。

Infection of eukaryotic host cells with intracellular pathogens is a well-coordinated process. It includes adhesion and invasion of the host cell, establishment of a replicative permissive intracellular niche and the release of infectious progeny from the infected cell. Apart from the well-studied processes invasion and intracellular survival, egress from the host cell is crucial step during infection that has so far not been investigated in depth. Pathogens can leave the host cell by different pathways including lysis of the host cell or by non-lytic processes that result in egress of the pathogen without host cell death. Extrusion formation by Chlamydia species is an example for the latter one. It is currently not well understood how exit pathways are regulated and which factors trigger distinct exit strategies under certain conditions. Especially, the roles of sphingolipids as bioactive lipids regulating cellular pathways including signaling and secretion have not been addressed in the context of non-lytic bacterial egress. Preliminary data of my group suggest that sphingolipids control Chlamydia extrusion formation. In this proposal, we aim to close this knowledge gap by studying the emerging roles of sphingolipids in regulation of extrusion formation of the zoonotic pathogen C. psittaci as a model organism by controlling signaling pathways, membrane dynamics and/or expression and localization of bacterial proteins. Furthermore, the impact of sphingolipids on exit strategies of other pathogens will be studied.