被称为“超级细菌”的鲍曼不动杆菌，极易对碳青霉烯类抗生素耐药。研究证实生物被膜态的细菌，有更强的耐药性和体外存活能力。细菌的双组份系统、群体感应（Quorum sensing，QS）及菌毛生成与其生物被膜的形成密切相关。本项目前期研究发现，抗菌肽Cec4，体内外毒性低，不仅对游离鲍曼不动杆菌有较好的杀菌效果，亦能抑制耐药菌生物被膜的形成，但目前抗菌肽如何抑制及清除细菌生物被膜的潜在机制尚不清楚。因此，通过从200株临床菌株中，筛选出生物被膜形成能力强的菌株；通过转录组和蛋白组关联分析，比较抗菌肽Cec4作用前后生物被膜态耐药菌形成生物被膜相关基因表达的差异，并鉴定与Cec4直接相互作用的蛋白，以期发现Cec4抑制生物被膜态耐药菌的关键分子及信号通路；通过对候选基因的敲出及回补实验，开展生物被膜表型及功能研究，证实Cec4抑制耐药菌生物被膜的潜在机制，最终为抗菌肽的药物研发提供理论支持。

It is well known that Acinetobacter baumannii is referred to as "super bacteria" with tending to carbapenem antibiotics resistance, and the bacteria in the biofilm state have stronger drug resistance and survivability in vitro. The bacterial two-component system, quorum sensing (QS) and fimbriae formation are closely related to the formation of its biofilm. The preliminary study of this project found that the antibacterial peptide Cec4 has low toxicity in vivo and in vivo. It not only has a good bactericidal effect on planktonic Acinetobacter baumannii, but also can inhibit the formation of its biofilm. However, the underlying mechanism of how antimicrobial peptides inhibit and remove bacterial biofilms is unclear. Therefore, strains with strong biofilm formation ability were screened from 200 clinical strains. Through transcriptome and proteomic correlation analysis, the differences in the expression of genes related to biofilm formation in biofilm resistant bacteria before and after the treatment of Cec4 were compared, and the proteins directly interacting with Cec4 will be identified, in order to discover the key molecules and signaling pathways of Cec4 inhibiting the biofilm formation of biofilm resistant bacteria. The phenotype and function of the biofilm will be studied by knocking out and supplementing the candidate genes, and the potential mechanism of Cec4 inhibiting the biofilm of drug-resistant bacteria will be confirmed, finally providing theoretical support for the drug development of antimicrobial peptides.