【摘要】 目的探讨calcineurin A基因(CnaA)对马尔尼菲篮状菌致病力的影响。方法通过观察CnaA基因缺陷菌株(ΔcnaA)形态发生、细胞壁完整性、压力应激、与巨噬细胞共培养后的生长情况,并构建动物感染模型以明确ΔcnaA敲除株致病力特点。结果ΔcnaA敲除株在形态发生及细胞壁完整性等方面存在缺陷;与巨噬细胞共孵育的ΔcnaA的分生孢子迅速被吞噬,相比于wild-type,被吞噬24 h后的ΔcnaA菌株生长速度较慢,在48 h时,巨噬细胞内的ΔcnaA菌株大部分被杀灭并分解;ΔcnaA感染的小鼠死亡率及组织菌载量较wild-type明显降低。结论 CnaA在马尔尼菲篮状菌的致病力中发挥重要的调控作用。更多还原

【Abstract】 Objective To investigate the effects of calcineurin A from T. marneffei on pathogenicity. Methods The morphogenesis, cell wall integrity, external stress responses, growth of co-cultured with macrophages, and constructed animal infection model were observed to determine the roles of the CnaA on the pathogenicity of T. marneffei. Results Deletion of the CnaA gene in T. marneffei resulted in a strain with significant defects in morphogenesis, cell wall integrity, and resistance to various stressors. The conidia of ΔcnaA strain co-incubated with RAW264.7 macrophages were rapidly phagocytosed. By 24 h, the ΔcnaA strain showed much slower growth than the wild-type cells. At 48 h, very few ΔcnaA strain remaining in macrophagesshowed that most of the ΔcnaA strain had been killed and degraded. In the infected mouse model, the mortality and tissue fungi burden of ΔcnaA mutant infected mice were significantly lower than those of wild-type. Conclusion CnaA of T. marneffei plays a key role in controlling fungal morphogenesis and the response to internal and external stresses, as well as in the host immune response and fungal pathogenicity.更多还原