光滑念珠菌在吞噬细胞内的生存能力在其免疫逃逸及致病过程中起重要作用，但具体调控机制未明。前期研究中我们发现光滑念珠菌在吞噬细胞内的生存能力和菌株DNA修复过程密切相关，且该过程需要CK2β亚基（由Ckb1/2基因编码）参与；同时Ckb1/2参与组蛋白H4S1磷酸化进而可能影响DNA修复过程。因此我们推测：光滑念珠菌Ckb1/2通过调控组蛋白H4S1磷酸化介导DNA修复从而维持其在吞噬细胞中生存。本课题拟先验证光滑念珠菌DNA修复过程在菌株维持吞噬细胞内生存中的作用；再通过构建Ckb1/2敲除、回复、过表达菌株及免疫共沉淀技术，明确Ckb1/2在DNA修复及H4S1磷酸化中的作用；通过突变H4S1位点和染色质共沉淀，研究H4S1磷酸化对DNA修复的影响；最后合成CK2β亚基抑制物，探讨其治疗念珠菌病的可能。本课题将首次明确光滑念珠菌组蛋白修饰与致病的联系，对临床寻找新的药物靶点具有重要意义。

The ability of Candida glabrata to maintain survival in phagocytic cells plays an important role in pathogenesis, however the regulatory mechanism is still unknown. In previous studies, we found that the survival of Candida glabrata in phagocytes is closely related to DNA repair ability, and the CK2β subunit (encoded by the Ckb1/2 gene) participates in this process; at the same time, Ckb1/2 participates in the phosphorylation of histone H4S1 and may affect DNA repair. Therefore, we propose that Candida glabrata Ckb1/2 mediates DNA repair by regulating histone H4S1 phosphorylation to maintain survival in phagocytes. This project intends to clarify the DNA repair process of Candida glabrata in maintaining survival in phagocytes first, then to clarify the role of Ckb1/2 in DNA repair and H4S1 phosphorylation by constructing Ckb1/2 knockout, recovery and overexpression strains and co-immunoprecipitation techniques; through mutation the H4S1 site and chromatin co-precipitation technique to determine the effects of H4S1 phosphorylation on DNA repair and survival in phagocytic cells. Finally, CK2β subunit inhibitors will be synthesized to study its role in reducing survival in phagocytes. This project will clarify the relationship between histone modification and pathogenicity in Candida glabrata for the first time, and explore the possibility of CK2β subunit inhibitors in the treatment of candidiasis, which will provide theoretical and experimental basis for the development of new drug targets.