鲍曼不动杆菌通过基因组突变及从外界获得耐药基因快速产生包括碳青霉烯类在内的几乎所有抗菌药物耐药，给全球抗感染治疗带来重大挑战。在我国鲍曼不动杆菌最主要的碳青霉烯耐药机制为获得OXA-23耐药基因，然而OXA-23基因在碳青霉烯耐药鲍曼不动杆菌(CRAB)中优势地位如何形成尚不明确，尤其是极易快速传播的质粒介导OXA-23基因。前期研究已获得携带OXA-23质粒的体外突变株和双拷贝质粒株。本研究拟将携带OXA-23质粒转入鲍曼不动杆菌标准株和临床分离株，在碳青霉烯抗生素压力下进行体内外传代获得更多突变株，通过比较基因组研究，发现调控进化的关键突变位点；结合上位效应、转录组和代谢组学，阐明关键突变位点在协同进化中的作用；通过携带OXA-23双拷贝质粒鲍曼不动杆菌在多种条件下耐药性、适应性和转录组学研究，揭示OXA-23双拷贝质粒在鲍曼不动杆菌协同进化中的作用。为CRAB耐药控制提供全新策略。

Acinetobacter baumannii rapidly develops almost all antimicrobial resistance, including carbapenems, through genomic mutations and acquired resistance gene, posing significant challenges to global anti-infective treatment. The most important carbapenem resistance mechanism in Acinetobacter baumannii in China is to obtain OXA-23 resistance gene, but how the dominant position of OXA-23 gene is formation in carbapenem-resistant A. baumannii (CRAB), that is still unclear, especially for OXA-23 plasmids that are highly prone to rapid spread. Previous studies have obtained in vitro mutant carrying the OXA-23 plasmid and double copy OXA-23 plasmid strains. This study intends to transfer the OXA-23 plasmid into the standard strain and clinical isolate of A. baumannii, and obtain more mutants in vitro and in vivo under the pressure of carbapenem antibiotics, through comparative genomic studies, found key evolution regulation mutation sites; using epistasis, transcriptome, and metabolomics to elucidate the role of key mutations in co-evolution; study resistance, fitness and transcriptomics by carrying the OXA-23 double-copy plasmid A. baumannii under a variety of conditions revealed the role of the OXA-23 double copy plasmid in the co-evolution of A. baumannii. Provide a new strategy for CRAB resistance control.