Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis
Feng Yang, Hui Lu, Hao Wu, Ting Fang, Judith Berman, Yuanying Jiang
Abstract
Candida parapsilosis is an emerging human fungal pathogen, especially prevalent in neonates. Aneuploidy, having uneven numbers of chromosomes, is a well-known mechanism for adapting to stress in Candida albicans, the most common human fungal pathogen. In this study, we exposed C. parapsilosis to two very different drugs and selected for rare cells that grew in one of the drugs. We found that the majority of isolates that grew in the drugs had acquired an extra copy of one of several aneuploid chromosomes and that specific aneuploid chromosomes appeared in several independent cell clones. Importantly, an extra copy of chromosome 6 was detected following selection in either one of the drugs, and this extra chromosome conferred the ability to grow in both drugs, a property called cross-adaptation, or cross-tolerance. Thus, this study highlights the genome plasticity of C. parapsilosis and the ability of an extra copy of a single chromosome to promote cell growth in the presence of more than one drug.