Mackey Anna I, Fillinger Robert J, Hendricks P Shane, Thomson Gregory J, Cuomo Christina A, Bennett Richard J, Anderson Matthew Z
Department of Microbiology, The Ohio State University, Columbus, OH, 43210, USA.
Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA.
Nat Commun. 2025 Apr 6;16(1):3287. doi: 10.1038/s41467-025-58457-3.
Inaccurate chromosome segregation can lead to the formation of aneuploid cells that harbor an imbalanced complement of chromosomes. Several fungal species are not only able to tolerate the detrimental effects of aneuploidy but can use it to adapt to environmental pressures. The fungal pathobiont Candida albicans frequently acquires supernumerary chromosomes that enable growth in the presence of antifungal drugs or in specific host niches, yet the transcriptional changes associated with aneuploidy are not globally defined. Here, a karyotypically diverse set of C. albicans strains revealed that expression generally correlated with gene copy number regardless of the strain karyotype. Unexpectedly, aneuploid strains shared a characteristic transcriptional profile that was distinct from a generalized environmental stress response previously defined in aneuploid yeast cells. This aneuploid transcriptional response led to altered growth and oxidative balances relative to euploid control strains. The increased expression of reactive oxygen species (ROS) mitigating enzymes in aneuploid cells reduced the levels of ROS but caused an acute sensitivity to both internal and external sources of oxidative stress. Taken together, our work demonstrates common transcriptional and phenotypic features of aneuploid C. albicans cells with consequences for infection of different host niches and susceptibility to environmental stimuli.
染色体分离不准确会导致非整倍体细胞的形成，这些细胞具有不平衡的染色体组成。几种真菌不仅能够耐受非整倍体的有害影响，还能利用它来适应环境压力。真菌病原体白色念珠菌经常获得额外的染色体，使其能够在抗真菌药物存在的情况下或在特定宿主生态位中生长，然而与非整倍体相关的转录变化尚未得到全面定义。在这里，一组核型多样的白色念珠菌菌株表明，无论菌株核型如何，表达通常与基因拷贝数相关。出乎意料的是，非整倍体菌株共享一种独特的转录谱，该转录谱与先前在非整倍体酵母细胞中定义的一般环境应激反应不同。这种非整倍体转录反应导致相对于整倍体对照菌株，生长和氧化平衡发生改变。非整倍体细胞中活性氧（ROS）缓解酶的表达增加降低了ROS水平，但导致对内部和外部氧化应激源的急性敏感性。综上所述，我们的工作证明了非整倍体白色念珠菌细胞的共同转录和表型特征，这些特征对不同宿主生态位的感染和对环境刺激的易感性具有影响。
