Discovery of the Diploid Form of the Emerging Fungal Pathogen .

The new multidrug-resistant pathogen 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 . Haploid and diploid cells of 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 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 to environmental changes. Our findings shed new light on the biology and pathogenesis of this emerging fungal pathogen.