创烧伤导致皮肤软组织缺损常伴细菌感染，引起创面迁延不愈。抗生素广泛应用导致耐药日趋严重，给临床治疗带来挑战。噬菌体的少数临床研究提示其效果显著，但伦理学限制了进一步应用。深入了解噬菌体控制宿主菌的机制，以此筛选新的抗菌药物或靶点，是当前研究热点之一。申请人前期转录组学测序系统性分析噬菌体-宿主菌的相互作用，筛选出多个未见报道的噬菌体控制基因；研究显示铜绿假单胞菌噬菌体PaP3基因产物Gp68显著抑制宿主菌生长速度，可能具有理想抗菌作用，但作用机制和应用尚待研究。本项目拟进一步研究Gp68对宿主菌的影响；通过转录组学测序等生信手段结合Crispr/cas9技术敲除/回补验证Gp68作用的靶基因；并通过基因报告系统、CHIP-seq和EMSA等技术研究Gp68作用的分子机制；最后通过动物模型探索Gp68在抗感染方面的应用。本研究将揭示Gp68影响细菌的机制，为临床治疗创面感染提供新思路。

Bacterial infections often accompany soft tissue defects caused by trauma or burn. While antibiotic resistance is becoming more and more dangerous, the development of new antibiotics is facing tons of difficulties. Phage has proved significant clinical effects through several trials, but ethics committees all over the world limit its more extensive application. Thus, it is becoming a hot topic to screen of new antibacterial drugs or targets from phages by understanding the interactions between phages and its hosts. Based on the transcriptomics study of phage phage-host bacteria interactions, this project screened out some unreported phage core control genes (clusters). The prophase experiments showed significant inhibition of host Pseudomonas aeruginosa PA3 strain from its phage PaP3 gene product Gp68. And the RNA-seq revealed that Gp68 unexpectedly up-regulated the host genes, which raised our interests. This project intends to study the phenotype of inhibition from Gp68 further; to validate the target genes of Gp68 through bioinformatics combined with Crispr/cas9 technology; to explore the molecular mechanism of Gp68 controlling its host through the gene reporting system, CHIP-seq, and EMSA, etc.; and make preliminary exploration of the application against infections though animal infection model. The research is expected to reveal a new control mechanism of phage in its hosts and will also provide ideas for the exploration of other new antibacterial drugs.