中文摘要
抗生素耐药性已经严重威胁公共健康,因此寻找新型抗生素是目前医疗领域亟待解决的问题。群体感应抑制剂(Quorum Sensing Inhibitors)以细菌群体感应系统为作用靶点,调控一系列基因进行特异性表达,减少毒力因子的产生和释放,干扰细菌生物被膜形成,阻断群体感应信号级联效应,但不会对细菌生存产生压力,因此不易产生耐药性,为人类提供了一种新型抗菌途径,被视为具有抗菌药物发展潜力的新策略。本项目利用基因组重排技术(Genome Shuffling)进行2株深海细菌基因组融合育种,构建重组细菌,采用群体感应抑制活性筛选模型及LC-MS/MS结构检索排重法,实现1株海洋来源重组细菌中具有群体感应抑制活性的新型药物先导化合物的挖掘,并对其机制探究,为后期群体感应抑制类抗生素的研发奠定理论基础,该研究在海洋微生物细菌耐药性先导化合物研究领域具有创新性、前沿性和竞争性,具重要的科学研究价值。
英文摘要
Emergence of antibiotic-resistant pathogenic bacteria is now a global threat for public health. Therefore, there is an urgent need to find novel antibiotics against these resistant bacteria in the medical field. Quorum sensing inhibitors act on bacterial quorum sensing system to control the specific expression of a series of genes, reduce the generation and release of virulence factors, interfere with the formation of Biofilm and block the quorum sensing signal cascade effect. However, quorum sensing inhibitors do not affect bacterial survival and thus may avoid drug-resistance problems. This method provides a novel antibacterial treatment and is considered as a new potential strategy for the development of antimicrobial agents. This project uses genome shuffling technology, screening model of quorum sensing inhibitors, and LC-MS/MS method to find novel quorum sensing inhibitors in the 1 recombinant marine bacteria and studies their mechanisms of action. This study provides a theoretical basis for the later development of novel antibiotics, exhibits obvious novelty, frontier, and competitiveness, and has important scientific significance.
