ESX-1分泌系统在结核杆菌的致病性中起关键作用,但为其体外生长非必需。抑制ESX-1分泌系统既可以降低结核杆菌的致病性和细胞内生存能力，实现治疗结核病的目的，同时又降低了对病原菌的选择性压力及耐药性突变的发生率。因而，ESX-1分泌系统成为极具潜力的新型抗结核药物的靶标。在我们的前期工作中，筛选到了ESX-1分泌系统抑制剂IMB-FBZ。该化合物可以有效抑制病原菌在细胞内的生存，但并不抑制病原菌体外生长。本课题拟深入研究IMB-FBZ的作用机制，开展其抗菌活性及耐药性发生率等研究工作，系统评价ESX-1分泌系统抑制剂作为不易诱导耐药的抗结核药物的可行性，为建立抗结核药物研发新策略以及发展创新性抗结核候选药物奠定基础。

ESX-1 secrete system is crucial for virulence in Mycobacterium tuberculosis but is not required for growth in vitro.Supressing this system can not only reduce the virulence of Mycobacterium tuberculosis and intracellular survival,but decrease the selective pressure to pathogen mycobacteria and the incidence of drug resistance mutation.Therefor,ESX-1 secrete system was of a great potentiality as a novel target of antituberculosis drugs.In our previous works,we screened the inhibitor of ESX-1 secrete system IMB-FBZ.This compound effectively inhibited the pathogen's survival in vivo but not inhibit the growth of pathogen mycobacteria.Our project aimed at researching the mechanism of IMB-FBZ,antibact-.erium activities and incidence of drug resistance to evaluate the feasibility of the inhibitor of ESX-1 as antituberculosis drugs that is not easy to induce drug resistance.It will lay the foundation for establishing the new theory of the development of antituberculosis drugs and develop innovative antituberculosis candidate drugs.