多重耐药鲍曼不动杆菌（MDRAB）分离率和感染率逐年攀升，MDRAB感染三种主要有效治疗药物（替加环素、多粘菌素和舒巴坦包括舒巴坦制剂）的耐药性迅速增加，出现对现有抗菌药物均耐药的全耐药菌，给抗感染治疗带来严峻的挑战。现有耐药机制研究，大多着眼于体外耐药研究，但体外耐药并不能真实反映体内情况。我们在前期研究中已获得MDRAB对上述三种抗菌药物体外阶梯诱导耐药株，已明确耐药株耐药突变情况。本研究拟以胎牛血清为诱导培养基，进行细菌适应性进化和耐药进化研究，以动物模型为基础，结合抗生素诱导，整合利用二代测序和三代测序技术鉴定参与体内适应性进化和耐药进化的新基因及新机制。收集临床进化分离株，研究人体体内进化过程，利用体内转录组学技术，明确MDRAB体内特异性表达基因，为抗生素研发提供潜在的靶标。结合适应性代价和毒力变化，预测MDRAB感染的流行趋势，为MDRAB治疗及耐药控制策略提供新的方案。

The isolation rate and infection rate of multi-drug resistant Acinetobacter baumannii (MDRAB) were increased every year. The resistance rate of three drugs (tigecycline, colistin and sulbactam) which were active against MDRAB were rapid emerged. The emergement of Pan drug resistant bacteria made treatment difficult. Current resistance mechanism research focused on in vitro resistance, and ignored the difference between in vivo and in vitro. Previously, we obtained the strain resistant to three drugs, respectively. The resistance mutations among the strains were identified. This study would perform adaptive evolution and resistance evolution in serum and use animal model and antibiotics induction to identify the novel genes and mechanisms involved in adaptive evolution and resistance evolution in vivo by the second sequencing technology and the third sequencing technology. We also collected the clinical isolates to study the in vivo evolution procedure in human. The study also explored the differential expressed genes in vivo using in vivo transcriptome to provide potential target for antibiotic research and development. At last, the study would combined fitness cost and virulence alteration to predict the clinical trends of MDRAB infections, and to suggest the new treatment and resistance control option.