Candida auris is a newly emerging pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time-frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.Introduction 1 A current, major concern in medical mycology is the emergence of the multidrug-resistant 2 pathogen Candida auris. This species was named according to its first identification as an isolate 3 from the ear canal of a Japanese patient in 2009. 1 Since then, it has rapidly become a major 4 healthcare threat with hospital outbreaks occurring worldwide. [2][3][4] Most C. auris isolates also 5 show high levels of resistance to antifungal drugs, including azoles, echinocandins, 5-flucytosine, 6 and polyenes (amphotericin B). 5,6 C. auris is also difficult to eradicate from hospital intensive 7 care wards and as a skin colonizer it can apparently be transmitted from patient to patient. 4 8 Whole genome sequencing (WGS) of C. auris isolates has indicated that there are at least 9 four distinct geographical clades of this species; East Asia (Japan, Korea), South Asia (India, 10 Pakistan), South Africa, and South America (Venezuela). 6 Clades differ by tens of thousands of 11 single nucleotide polymorphisms (SNPs) from each other, however, within each clade isolates 12 are almost indistinguishable from each other on a DNA sequence level. 5-7 This suggests that the 13 C. auris population structure is characterized by distinct and highly variable clades that are 14 distributed worldwide and almost non-variable clonal expansions of a single genotype within 15 individual outbreaks. 3,4 The origin(s) of the strong variability between and the minor variability 16 within clades are currently unknown. 17 Polyploidy, aneuploidy, and gross chromosome rearrangements have been recognized 18 drivers of genetic diversity in pathogenic and non-pathogenic fungi for some time. 8-12 In 19 pathogenic yeasts, such as C. albicans, mechanisms for ploidy shifts and chromosome 20 rearrangements have been described, and their importance for adaptation to environmental 21 stresses and host niches, as well as for developing resistance to antifungal drugs has been 22 identified. 13-17 23Here, we characteri...