铜绿假单胞菌是一种临床难对付的重要条件致病菌，近年来多药耐药发展迅速，急需新型抗铜绿假单胞菌药物。传统抗菌药物通过抑制细菌生长或杀菌发挥作用，易于产生耐药性，而靶向细菌毒力因子如绿脓菌素的新型抗菌药物通过消弱细菌致病力，借助人体自身免疫力清除细菌，不易产生耐药选择压力，具有减少或延缓耐药性产生的优势。mvaT、mvaU编码铜绿假单胞菌中的组蛋白样类核结构蛋白，我们的前期研究发现， mvaT或mvaU单敲除时绿脓菌素表达升高，而两者双敲除时绿脓菌素表达完全缺失，并且可用携带mvaT或mvaU的质粒回复绿脓菌素的产生。推测mvaT mvaU双敲除通过完全不同于mvaT或mvaU单敲除的方式抑制或截断了绿脓菌素的合成。本课题拟就mvaT mvaU双敲除引起绿脓菌素产生缺失的机制进行研究，以期发现调控绿脓菌素产生的关键因素，发展新型抗铜绿假单胞菌药物研发靶标，应对日益严重的铜绿假单胞菌耐药。

Pseudomonas aeruginosa is an important opportunistic pathogen in clinic. The rapid increase of P. aeruginosa resistant to multiple drugs in recent years pushes us to explore new anti-pseudomonas drugs. Bacteria are easy to develop resistance to traditional antibacterial drugs as the drugs inhibit or kill the bacteria. New antibacterial drugs targeting virulence factors like pyocyanin have the advantage of decreasing or slowing the appearance of resistance due to their low effect on bacterial survival. mvaT and mvaU encode histone-like nucleoid structuring proteins in P. aeruginosa. Our previous results demonstrated that different as mvaT or mvaU single knockout strains, which demonstrated increased production of pyocyanin, mvaT mvaU double knockout strains showed elimination of pyocyanin production, and the elimination of pyocyanin in the double knockout strains can be complemented by plasmids carrying mvaT or mvaU. The results suggested that pyocyanin synthesis was inhibited or eliminated through mvaT mvaU double knockouts by mechanisms totally different as mvaT or mvaU single knockout. In the present study, we aimed at studying the mechanism of pyocyanin elimination caused by mvaT mvaU double knockouts in P. aeruginosa, in order to find critical factors for regulating pyocyanin production, and develop new targets for anti-pseudomonas drugs to fight back against the increasing resistance to pseudomonas.