耐药致病菌引起的感染性疾病严重危害人类健康，研制不易诱导耐药的新型抗菌分子成为抗菌药物研发的当务之急。干扰细菌分裂或抑制细菌群体感应系统的抗毒力策略，可有效缓解细菌的生存压力，降低其耐药性。新近研究表明，FtsZ蛋白是干扰细菌细胞分裂、不易诱导细菌耐药的理想靶标；QseC是抑制G-菌毒力因子生成、不易诱导细菌耐药的理想靶标。本课题从全新的思路入手，将干扰细菌分裂的FtsZ抑制剂药效团与抑制G-菌群体感应系统QseC的抗毒力配体LED209相偶联，首次创制出全新的具有特异干扰细菌分裂、降低细菌毒力的低耐药双靶标抗G-菌分子，并对该分子展开G-细菌靶向特异性、分裂能力、毒力分泌、体内外抗菌活性及作用机理等方面研究。研究结果将为抗耐药菌药物的研制提供新思路和新策略，为耐药细菌感染治疗探索新的路径。

Infectious diseases caused by multidrug resistant bacteria have become a serious threat to human beings. Development of new antibiotic drugs with low resistance rate, is an urgent job for the research and development of novel antibiotic agent. The strategies on interfering with bacterial division or anti-virulence by inhibiting bacterial quorum sensing system, can effectively alleviate the survival pressure of bacteria and reduce their resistance on drugs. Recent studies have shown that FtsZ protein is an ideal target on inhibiting bacterial cell division and reducing resistance. And QseC is another ideal target on decreasing G- bacterial virulence production and lowering resistance. In this project, we firstly design and synthesis some novel low-resistance moleculars with double targets by conjugating FtsZ inhibitors pharmacophore and QseC ligand LED209, which could specifically block bacterial division and inhibit the expression and release of virulence genes in G- bacteria. Then we will evaluate the characters and function of these moleculars on targeting effects, G- bacterial division ability, G- bacterial virulence production, the antibacterial activity in vitro and in vivo, and further explore the underlying antibacterial mechanisms. The results will provide novel strategies for drug development in anti-multidrug resistant bacteria and new paths for the treatment of drug-resistant bacterial infections.