The role of phospholipase PlaF mediated membrane alterations for Pseudomonas aeruginosa virulence adaptations (A02#)

该项目解决了由人类病原体铜绿假单胞菌产生的细胞内磷脂酶A如何能够发挥各种有助于毒力适应的细胞反应的问题。这种名为PlaF的酶改变了铜绿假单胞菌的内源性膜脂组成，并调节了几种必要的和毒力相关的途径，其机制尚不清楚。在这里，我们将研究膜蛋白复合物的组装，其形成依赖于PlaF蛋白的相互作用，并确定膜磷脂组成的变化。重组膜复合物的体外实验将用于阐明与先前鉴定的蛋白质和脂质效应物相互作用的分子细节及其调节PlaF生化功能的作用。预期的结果应该为脂质降解途径在膜生物发生和毒力中的功能提供新的见解。

The project addresses the question how an intracellular phospholipase A produced by the human pathogen Pseudomonas aeruginosa can exert a variety of cellular responses which contribute to virulence adap-tation. This enzyme named PlaF alters the endogenous membrane lipid composition and regulates several essential and virulence-related pathways in P. aeruginosa by still unknown mechanisms. Here, we will study the assembly of membrane protein complexes whose formation is dependent on PlaF:protein interactions and determine alterations of the membrane phospholipid composition. In vitro experiments with reconstituted membrane complexes will be used to elucidate molecular details of the interactions with the previously identified protein and lipid effectors and their effects for regulating the biochemical function of PlaF. The anticipated results should provide novel insights into the function of lipid degradation pathways for membrane biogenesis and virulence.