铜绿假单胞菌是引起临床获得性感染及诱发肺部纤维状病变的主要致病菌之一。它在生长过程中能分泌多种胞外多糖来适应和抵抗外界环境的变化。藻酸盐（Alginate）作为一种重要的表面多糖，在引起肺纤维囊肿病、病原菌生物膜的形成以及毒力表型的变化中起着非常重要的作用。尽管藻酸盐的合成途径在过去的研究中得以阐述，但对介导该途径中的某些重要蛋白的调控机制及其功能的认识还相当有限。本项目将运用ChIP-seq 和RNA-seq 高通量测序技术，系统地探讨参与藻酸盐合成途径中5个蛋白（Vfr, AlgP, AlgB, CysB和RpoN）的整体调控途径。同时在全基因组水平上寻找与藻酸盐合成相关的蛋白，来揭示细菌生物被膜形成、毒性基因调控、以及耐药性产生等方面的分子机制。研究结果将有助于了解铜绿假单胞菌的致病机制和抗药性形成机理，为控制铜绿假单胞菌的感染以及为开发针对以该途径中的蛋白为靶点的新型抗菌。

Pseudomonas aeruginosa is one of the major pathogen causing clinical acquired infection and inducing lung infection in cystic fibrosis patients. A vast range of extracellular polysaccharides are produced by P.aeruginosa in order to adapt to and thrive in diverse environmental niches. Alginate as an important exopolysaccharide that plays important roles in cystic fibrosis infection, biofilm formation and virulence phenotypes transition. Although the pathways of alginate biosynthesis have been determined and proposed in the past, the regulatory mechanisms and functions of some proteins involved in the production of bacterial alginate have yet to be fully elucidated. In this proposal, we will systematically investigate the global pathways of five proteins (Vfr, AlgP, AlgB, CysB and RpoN) using ChIP-seq and RNA-seq methods. Meanwhile, we will look for other proteins related to alginate biosynthesis from the whole Pseudomonas genome to reveal how biofilm formation, virulence gene regulation and antibiotic resistance. These results will provide us important information on how to control the pathogenecity of P. aeruginosa, which might lead to the development of new antimicrobiol compounds that specifically target these proteins in the future.