慢性难治性皮肤溃疡及褥疮与铜绿假单胞菌生物被膜形成密切相关，在生物被膜形成过程中密度感应系统发挥非常重要的作用，在自然基金资助下，我们系统的研究了铜绿假单胞菌密度感应信号系统对生物被膜形成的影响。在体外率先发现铜绿假单胞菌的分解代谢物阻遏调控蛋白（Crc）突变株比其野生型菌株有较高水平的的代谢活性，能够抵抗抗菌肽的作用，Crc突变菌可过量合成绿脓素，同时又丧失了与耐药性相关的涌动能力，影响早期生物被膜的形成。由此可以推断铜绿假单胞菌的分解代谢物阻遏调控蛋白能够影响细菌毒性因子的释放，且影响生物被膜形成的全过程。为了证实此假设我们设计制作大鼠慢性皮肤溃疡模型，播种野生型及Crc基因突变的铜绿假单胞菌，探讨Crc突变对慢性创面生物被膜形成的影响，同时明确不同生物被膜感染对创伤愈合的影响，深入了解野生株和突变株在细菌毒力上的差异，期待研发出控制生物膜形成或瓦解生物膜的药物及治疗方案。

Bacterial colonization and infection are key factors in compromised wound healing,particularly in chronic wounds.Reported in the literature refractory chronic skin ulcers and bedsores are closely related to Pseudomonas aeruginosa biofilm formation.Quorum sensing contributes much to biomembrane formation.In the support of National Natural Science Foundation, we investigated the regulation of Pseudomonas aeruginosa quorum sensing system on biomembrane formation．For the first time we found the Pseudomonas aeruginosa catabolite repression control protein( Crc) mutant has a higher fitness compared to the wild-type P.aeruginosa in vitro.The catabolite repression mutant strains with high metabolic activity show high resistantance to the treatment of antimicrobial peptides. P. aeruginosa Crc mutant is able to produce more pyocyanin and losts the movement ability associated with drug resistance. Moreover, the early stage biomembrane formation of P. aeruginosa Crc mutant is less than its wild-type strain. It can be inferred the Pseudomonas aeruginosa catabolite repression control protein（Crc）can affect the release of toxicity factor and affect the whole process of biofilm formation. We designed rat model of chronic skin ulcers in order to confirm this hypothesis. We discuss the influence of the Crc mutation for chronic wound biomembrane formation through the wild type and Crc gene mutation of pseudomonas aeruginosa.For improving treatment of chronic infection induced by biomembrane, we need to investigate the characteristics of the biomembrane in the animal model suffered from different types of chronic infection.However, the mechanism how Crc affects the P. aeruginosa pqs QS system in medium supplemented with different carbon sources is not clear, and the study of how Crc control long-term formation of biomembrane and host immunity. Further study coud reveral how different biomembrane affact would healing.and what is the difference between mutant and wild-type.Based on our previous study, the purpose of this work is to develop some drugs or treatments to control formation and collapse of biomembrane.