Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200086, China.
Genetics. 2021 Jun 24;218(2). doi: 10.1093/genetics/iyab056.
Candida albicans is a prevalent human fungal pathogen. Rapid genomic change, due to aneuploidy, is a common mechanism that facilitates survival from multiple types of stresses including the few classes of available antifungal drugs. The stress survival of aneuploids occurs despite the fitness costs attributed to most aneuploids growing under idealized lab conditions. Systematic study of the aneuploid state in C. albicans has been hindered by the lack of a comprehensive collection of aneuploid strains. Here, we describe a collection of diploid C. albicans aneuploid strains, each carrying one extra copy of each chromosome, all from the same genetic background. We tested the fitness of this collection under several physiological conditions including shifts in pH, low glucose, oxidative stress, temperature, high osmolarity, membrane stress, and cell wall stress. We found that most aneuploids, under most conditions, were less fit than their euploid parent, yet there were specific conditions under which specific aneuploid isolates provided a fitness benefit relative to the euploid parent strain. Importantly, this fitness benefit was attributable to the change in the copy number of specific chromosomes. Thus, C. albicans can tolerate aneuploidy of each chromosome and some aneuploids confer improved growth under conditions that the yeast encounters in its host niches.
白色念珠菌是一种常见的人类真菌病原体。由于非整倍体的存在,基因组的快速变化是一种常见的机制,有助于其从多种压力中存活下来,包括少数几类可用的抗真菌药物。尽管大多数非整倍体在理想的实验室条件下生长会带来适应性成本,但它们仍然能够在压力下存活。系统性地研究白色念珠菌的非整倍体状态受到缺乏全面的非整倍体菌株集合的阻碍。在这里,我们描述了一组来自相同遗传背景的二倍体白色念珠菌非整倍体菌株,每个菌株都额外携带了一条染色体的一个拷贝。我们在几种生理条件下测试了这个集合的适应性,包括 pH 值变化、低糖、氧化应激、温度、高渗透压、膜应激和细胞壁应激。我们发现,在大多数情况下,大多数非整倍体的适应性都不如它们的整倍体亲本,但在某些特定条件下,特定的非整倍体分离株相对于整倍体亲本菌株提供了适应性优势。重要的是,这种适应性优势归因于特定染色体拷贝数的变化。因此,白色念珠菌可以容忍每条染色体的非整倍体,并且一些非整倍体在酵母在其宿主小生境中遇到的条件下提供了更好的生长。