广泛耐药鲍曼不动杆菌是目前临床上最具威胁的“超级细菌”，多黏菌素是治疗该类耐药菌的首选药物。多黏菌素具有较强的毒副作用，抗菌增效剂可以增强多黏菌素的杀菌活性，从而能在相同疗效下降低多黏菌素的临床使用剂量，减少不良反应。我们在前期研究中，首次筛选到新型芳亚胺基噻唑类新化合物KJ1371，可以使多黏菌素抗鲍曼不动杆菌的MIC降低8-16倍。深入研究发现KJ1371可增加鲍曼不动杆菌对于多黏菌素的吸附量，这是第一次发现具有该机制的活性化合物。本课题聚焦于化合物KJ1371是如何增加鲍曼不动杆菌对于多黏菌素吸附量这一关键科学问题，研究KJ1371多途径增效多黏菌素的机制，找到相关靶标。我们还使用蛋白质组，转录组和基因随机突变体库筛选的方式，考察KJ1371其他增效机制。KJ1371多途径增效多黏菌素机制的阐明，将找到可以增强鲍曼不动杆菌对多黏菌素敏感性的靶标，为抗耐药菌药物研发提供新的思路和途径。

Polymyxin is the first-choice drug for the treatment of Extensively Drug Resistant Acinetobacter baumannii is most dangerous pathogens in clinic. Antibacterial synerists can promote the activity of Polymyxin which has the strong side effects. So, the same effects was reached with the less dosage of Polymyxin, which can reduce the adverse reaction of Polymyxin in clinic. In the previous work novel phenlimino-thiazolidine compound KJ1371 was screened which can reduce MIC of Polymyxin against Acinetobacter baumannii 8-16 folds. More research showed that KJ1371 can increase adsorption capacity of Acinetobacter baumannii to Polymixin which was discovered for the first time. This project focuses on the study of the pathway of the synergistic effect of KJ1371. In this study the mechanism and related target of the multipath synergistic effect of KJ1371 will be identified. The other mechanism of the synergistic effect of KJ1371 will be studied using proteomics, transcriptome and random gene mutant library screening methods. This study will identify the target which promote the sensitivity of Acinetobacter baumannii to polymyxin. This study also provides the new ideas and approaches for the development of drug against resistant bacteria.