BPSL1549毒力蛋白及O-GlcNAc糖链通过eIF4A蛋白调控类鼻疽伯克霍尔德军胞内感染机制的研究

类鼻疽伯克霍尔德菌（Bp）所致类鼻疽的误诊率和病死率极高，海南是我国发病率最高的地区。Bp分泌的毒力蛋白（BPSL1549）可与胞内真核蛋白翻译起始因子eIF4A蛋白互作，但Bp对宿主细胞的毒性机制仍不清楚。OGlcNAc糖基化是真核生物体内的一种蛋白翻译后修饰，研究发现O-GlcNAc严重影响败血症转归。本人以前研究表明eIF4A具有O-GlcNAc修饰。在类鼻疽中，BPSL1549和O-GlcNAc是否共同调控eIF4A功能，影响感染进程及宿主细胞生长繁殖？我们建立了Bp不同感染时间及感染复数的细胞模型，发现宿主多核细胞数量、BPSL1549表达量、O-GlcNAc糖基化水平和感染时间及复数呈正相关。本项目拟在蛋白水平探究BPSL1549和O-GlcNAc如何共同调控eIF4A功能并调控类鼻疽宿主细胞发展，结合临床，解析eIF4A在类鼻疽细胞模型中的功能，期望为类鼻疽的防治提供新策略。

Burkholderia pseudomallei (Bp) is the causative of melioidosis, Hainan island is regarded as a main endemic area in China. BPSL1549, secretion by Bp, can interaction with protein translation initiation factor eIF4A protein. But there is nothing known about the mechanism of virulence. O-GlcNAc is a post-translation modification in eucaryon, early study found that O-GlcNAc affected the outcome of sepsis seriously. eIF4A protein has O-GlcNAc modification in my early study. If BPSL1549 and O-GlcNAc can regulate the function of eIF4A in melioidosis? And if further affected the course of infection and the growth and reproduction of host cells?.In the early study, we found that the number of polynuclear cells, the expression level of BPSL1549, the level of O-GlcNAc level were positively correlated with the time and the MOI of infection. On this basis, we proposed that further study on the regulatory mechanism of BPSL1549 and O-GlcNAc on the fuction of eIF4A, and the mechanism on the development of melioidosis. And combine the clinical samples, reveal the important role of BPSL1549, O-GlcNAc, eIF4A in meliodisis, and find a new sttrategy for melioidosis prevention and cure.