广泛耐药鲍曼不动杆菌是目前临床上最有威胁的“超级细菌”，多粘菌素是治疗该类耐药菌的最后一道防线。但是多粘菌素具有较强的毒副作用，抗菌增效剂可以增强多粘菌素的杀菌活性，从而降低多粘菌素的临床使用剂量，减少不良反应。我们前期对天然源小分子化合物库进行了抗菌增效的筛选，从近4000个化合物中发现了具有长链不饱和脂肪烃的酚类化合物1030，可以使多粘菌素体外抗鲍曼不动杆菌模式菌株和临床分离株的最小抑菌浓度降低4-8倍；对实验室获得的自发耐药突变株也具有增效4-8倍的效果。同时发现单独使用1030对多种革兰氏阳性菌的混合感染也具有中等程度的抗菌活性。初步研究发现1030可增加鲍曼不动杆菌对于多粘菌素的吸附量。本课题将利用化学生物学、基因组学和蛋白质组学的方法，阐明其增效作用机制。同时通过发现具有长链不饱和脂肪烃的苯酚类结构的天然来源的、具有增效作用的多样性类似物，为新药开发打下物质基础。

Acinetobacter baumannii, is the most threatened "superbug" in the clinic at present, and polymyxin is the last line of defense of drug for the extensively drug resistant bacteria. However, polymyxin has strong toxic and side effects. The antibacterial synergist can enhance the bactericidal activity of polymyxin so as to reduce the clinical dosage of polymyxin and reduce the adverse reaction. Previously we have carried out an antiseptic synergistic screening for the natural compounds from small molecule compound library, phenolic compound 1030 with long chain unsaturated fatty acid was found from nearly 4000 compounds, could reduce the minimum inhibitory concerntration of polymyxin against Bauman’s Acinetobacter strains and clinical isolates by 4-8 times. It is also found that 1030 alone has a moderate degree of antibacterial activity against mixed infection of Gram-positive bacteria. These results were great interest to us. Our preliminary study found that 1030 can increase the adsorption capacity of Acinetoacter bauman for polymyxin. Our research will use the methods of chemical biology, genomics and proteomics to elucidate the mechanism of its synergism. The natural basis and synergistic diversity analogures of phenol structure with long chain unsaturated fatty hydrocarbons were found to lay the material foundation for new drug development.