Molecular Mycology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
Institut Pasteur, Université Paris Cité, INRAE, USC2019, Unité Biologie et Pathogénicité Fongiques, F-75015, Paris, France.
Nat Commun. 2022 Jul 23;13(1):4256. doi: 10.1038/s41467-022-31980-3.
Chromosomal instability caused by cell division errors is associated with antifungal drug resistance in fungal pathogens. Here, we identify potential mechanisms underlying such instability by conducting an overexpression screen monitoring chromosomal stability in the human fungal pathogen Candida albicans. Analysis of ~1000 genes uncovers six chromosomal stability (CSA) genes, five of which are related to cell division genes of other organisms. The sixth gene, CSA6, appears to be present only in species belonging to the CUG-Ser clade, which includes C. albicans and other human fungal pathogens. The protein encoded by CSA6 localizes to the spindle pole bodies, is required for exit from mitosis, and induces a checkpoint-dependent metaphase arrest upon overexpression. Thus, Csa6 is an essential cell cycle progression factor that is restricted to the CUG-Ser fungal clade, and could therefore be explored as a potential antifungal target.
细胞分裂错误导致的染色体不稳定性与真菌病原体中的抗真菌药物耐药性有关。在这里，我们通过对人类真菌病原体白色念珠菌中的染色体稳定性进行过表达筛选，来确定这种不稳定性的潜在机制。对大约 1000 个基因的分析揭示了 6 个染色体稳定性（CSA）基因，其中 5 个与其他生物体的细胞分裂基因有关。第六个基因 CSA6 似乎只存在于 CUG-Ser 分支的物种中，该分支包括白色念珠菌和其他人类真菌病原体。CSA6 编码的蛋白质定位于纺锤体极体，对于有丝分裂的退出是必需的，并且在过表达时会诱导依赖检查点的中期停滞。因此，Csa6 是一种必需的细胞周期进展因子，仅限于 CUG-Ser 真菌分支，因此可以作为一种潜在的抗真菌靶标进行探索。
