Effect of Replicative Aging on Cryptococcus neoformans

Cryptococcus neoformans (Cn) is an opportunistic fungal microorganism that causes life-threatening meningoencephalitis. During the infection, the microbial population is heterogeneously composed of cells with varying generational ages, with older cells accumulating during chronic infections. This is attributed to their enhanced resistance to phagocytic killing and tolerance of antifungals like fluconazole (FLC). Using RNA-seq, we investigated how transcriptomic changes in different aspects of metabolism contribute to age-associated FLC tolerance in Cn. To study the effects of replicative aging on the transcriptome of C. neoformans, we isolated young (0-3 generations) and old (10 generations) cells. Then, the transcriptomes of young and old cells were analyzed to identify ent gene expression.

新型隐球菌（Cryptococcus neoformans，简称Cn）是一类机会致病性真菌，可引发致死性脑膜脑炎。感染过程中，该微生物种群呈现异质性，由不同世代年龄的细胞构成，慢性感染阶段会出现老龄细胞的富集。该现象源于老龄细胞对吞噬细胞杀伤的抗性增强，且对氟康唑（fluconazole，简称FLC）等抗真菌药物具有耐受性。本研究通过RNA测序（RNA-seq）技术，探究了代谢多维度的转录组变化如何介导Cn中与年龄相关的氟康唑耐受性。为研究复制性衰老对新型隐球菌转录组的影响，我们分别分离了年轻细胞（0~3代）与老龄细胞（10代），随后对年轻与老龄细胞的转录组进行分析，以鉴定差异基因的表达。