鲍曼不动杆菌在感染部位存活、抵抗机体免疫清除的具体机制不明。GigA/GigB是鲍曼不动杆菌应对压力的重要调控因子。我们发现GigA/GigB基因敲除株的ABUW_1645基因表达上调、逆境生存力下降；基因回补可逆转此表型。ABUW_1645属于TetR调控家族，其表达下调可增强菌株对免疫清除的抵抗。据此推测，GigA/GigB通过下调ABUW_1645表达增强鲍曼不动杆菌抵抗免疫清除的能力。本研究拟构建GigA/GigB和/或ABUW_1645基因的敲除及表达株，在体外、细胞和体内三个层面验证该通路的调控作用和机制；从核酸和蛋白两个方面探索GigA/GigB对ABUW_1645的调控方式；通过转录组分析、结合已知毒力机制，识别并验证受ABUW_1645调控的毒力因子。阐明GigA/GigB-ABUW_1645通路在鲍曼不动杆菌抵抗免疫清除中的作用机制，将为新药和疫苗研发提供基础。

The clinical prognosis of multidrug resistant Acinetobacter baumannii infected patients is poor. Such situation should be associated with the bacterial host immune resistance. While, the mechanism is still unclear. It was well known that GigA/GigB served as a master regulator of stress response in Acinetobacter baumannii. Meanwhile, GigA/GigB also regulates varies functional genes, including ABUW_1645, one of the TetR family. We found that A. baumannii strain became weak in adverse situation with increased ABUW_1645 expression if GigA/GigB was koncked out. The GigA/GigB complementary strain of A. baumannii recovered its survivability and decreased ABUW_1645 expression. The reduced expression of ABUW_1645 was found able to help the strain to escape from immune elimination. Hence, we hypothesis the decreased expression of ABUW_1645 is regulated by GigA/GigB in A. baumannii to help the bacteria escape from host immune elimination. We plan to construct GigA/GigB and/or ABUW_1645 knock-out and complementary strains in A. baumannii, then use them for in vitro and in vivo test to confirm the regulation of GigA/GigB to ABUW_1645. We also will detail the regulation mechanism between GigA/GigB and ABUW_1645 in two aspects, interactions between protein-protein and RNA-protein. Thereafter we will identify the virulent factor in the downstream of ABUW_1645 via analyze the details of transcriptome. The aim of current proposal is to declare the regulator pathway of GigA/GigB and ABUW_1645, which will be important for the development of vaccine and new antibiotic against A. baumannii infections.