Discovery of the Diploid Form of the Emerging Fungal Pathogen Candida auris

The new multidrug-resistant
pathogen Candida auris was first described
in 2009 in Japan and has emerged in many countries
worldwide. This human fungal pathogen has long been considered a haploid
fungus. Here, we report the discovery of the diploid form and spontaneous
ploidy shifts in clinical isolates of C. auris. Haploid and diploid cells of C. auris differ in several aspects including growth rates, virulence, and
global gene expression profiles. For example, diploid cells exhibit
a slower growth rate than haploid cells in in vitro culture media; however, they are more virulent than haploid cells
in a mouse systemic infection model. Global transcriptional expression
analysis demonstrates that both haploid and diploid cells express
a set of ploidy-enriched genes, which are involved in the regulation
of metabolism, cell wall maintenance, translation and DNA replication,
and other important biological processes. Antifungal susceptibility
testing shows that haploid and diploid cells exhibit similar responses
when treated with a number of antifungals. Taken together, haploid
and diploid cells may have different fitness responses to diverse
niches, and ploidy changes could be an adaptive strategy of C. auris to environmental changes. Our findings shed
new light on the biology and pathogenesis of this emerging fungal
pathogen.

新发现的具有多重耐药性的病原体耳念珠菌（Candida auris）首次于2009年在日本被描述，并已在全球多个国家出现。该人类真菌病原体长期以来一直被认为是一种单倍体真菌。在本研究中，我们报告了耳念珠菌临床分离株中发现的二倍体形式及其自发倍性转变。耳念珠菌的单倍体和二倍体细胞在多个方面存在差异，包括生长速度、致病性和全局基因表达谱。例如，在体外培养介质中，二倍体细胞相较于单倍体细胞表现出较慢的生长速度；然而，在老鼠系统性感染模型中，它们相较于单倍体细胞具有更强的致病性。全局转录表达分析显示，单倍体和二倍体细胞均表达一系列倍性富集的基因，这些基因参与调节代谢、细胞壁维护、翻译和DNA复制等重要生物学过程。抗真菌敏感性测试表明，在多种抗真菌药物处理下，单倍体和二倍体细胞表现出相似的反应。综合来看，单倍体和二倍体细胞可能对不同的生态位具有不同的适应性反应，而倍性变化可能是耳念珠菌应对环境变化的适应性策略。我们的研究为这种新兴真菌病原体的生物学和发病机制提供了新的见解。