First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C . auris were isolated from distinct geographical locations. Although C . auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C . auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis . Infections and outbreaks caused by C . auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C . auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C . auris . Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C . auris infections.

The emerging human fungal pathogen Candida auris has been recognized as a multidrug resistant species and is associated with high mortality. This fungus was first described in Japan in 2009 and has been reported in at least 18 countries on five continents. In this study, we report the first isolate of C. auris from the bronchoalveolar lavage fluid (BALF) of a hospitalized woman in China. Interestingly, this isolate is susceptible to all tested antifungals including amphotericin B, fluconazole, and caspofungin. Copper sulfate (CuSO4) also has a potent inhibitory effect on the growth of this fungus. Under different culture conditions, C. auris exhibits multiple morphological phenotypes including round-to-ovoid, elongated, and pseudohyphal-like forms. High concentrations of sodium chloride induce the formation of a pseudohyphal-like form. We further demonstrate that C. auris is much less virulent than Candida albicans in both mouse systemic and invertebrate Galleria mellonella models.

This study describes a novel “white-gray-opaque” tristable phenotypic switching system in the human fungal pathogen Candida albicans, revealing additional complexity in this organism's ability to adapt to changing environments.

Morphological plasticity has historically been an indicator of increased virulence among fungal pathogens, allowing rapid adaptation to changing environments. Candida auris has been identified as an emerging multidrug-resistant human pathogen of global importance. Since the discovery of this species, it has been thought that C. auris is incapable of filamentous growth. Here, we report the discovery of filamentation and three distinct cell types in C. auris: typical yeast, filamentation-competent (FC) yeast, and filamentous cells. These cell types form a novel phenotypic switching system that contains a heritable (typical yeast-filament) and a nonheritable (FC-filament) switch. Intriguingly, the heritable switch between the typical yeast and the FC/filamentous phenotype is triggered by passage through a mammalian body, whereas the switch between the FC and filamentous phenotype is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote the FC yeast phenotype. Systemic in vivo and in vitro investigations were used to characterize phenotype-specific variations in global gene expression, secreted aspartyl proteinase (SAP) activity, and changes in virulence, indicating potential for niche-specific adaptations. Taken together, our study not only sheds light on the pathogenesis and biology of C. auris but also provides a novel example of morphological and epigenetic switching in fungi.