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.

Candida albicans , a commensal organism and a pathogen of humans, can switch stochastically between a white phase and an opaque phase without an intermediate phase. The white and opaque phases have distinct cell shapes and gene expression programs. Once switched, each phase is stable for many cell divisions. White–opaque switching is under a1–α2 repression and therefore only happens in a or α cells. Mechanisms that control the switching are unknown. Here, we identify Wor1 (white–opaque regulator 1) as a master regulator of white–opaque switching. The deletion of WOR1 blocks opaque cell formation. The ectopic expression of WOR1 converts all cells to stable opaque cells in a or α cells. In addition, the ectopic expression of WOR1 in a/α cells is sufficient to induce opaque cell formation. Importantly, WOR1 expression displays an all-or-none pattern. It is undetectable in white cells, and it is highly expressed in opaque cells. The ectopic expression of Wor1 induces the transcription of WOR1 from the WOR1 locus, which correlates with the switch to opaque phase. We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white–opaque switching.

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...

To mate, the fungal pathogen Candida albicans must undergo homozygosis at the mating-type locus and then switch from the white to opaque phenotype. Paradoxically, opaque cells were found to be unstable at physiological temperature, suggesting that mating had little chance of occurring in the host, the main niche of C. albicans. Recently, however, it was demonstrated that high levels of CO₂, equivalent to those found in the host gastrointestinal tract and select tissues, induced the white to opaque switch at physiological temperature, providing a possible resolution to the paradox. Here, we demonstrate that a second signal, N-acetylglucosamine (GlcNAc), a monosaccharide produced primarily by gastrointestinal tract bacteria, also serves as a potent inducer of white to opaque switching and functions primarily through the Ras1/cAMP pathway and phosphorylated Wor1, the gene product of the master switch locus. Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans. To mate, the human fungal pathogen Candida albicans must undergo a complex phenotypic change from a round “white” to large, elongated “opaque” cell. This involves the regulation of approximately 5% of the organism's genes. Surprisingly, this complex transition is not required for mating in other related yeast. Even more surprisingly, it was found that in vitro the mating-competent opaque phenotype was unstable at 37°C, the temperature of the host body. This observation led to a paradox. If C. albicans lives primarily in an animal host, physiological temperature would thwart mating, so where does C. albicans mate? This led to the suggestion that some physiological condition in the host niche stabilizes the opaque phenotype or even induces switching from white to opaque, so cells can mate. Recently, we demonstrated that the high concentrations of CO₂ found in tissue and the gastrointestinal tract induced switching from white to opaque and then stabilized the opaque phenotype. Here, we demonstrate that a second factor, N-acetylglucosamine (GlcNAc), a sugar released primarily by bacteria in the gastrointestinal tract, also induces the switch from white to opaque and stabilizes the opaque phenotype. We demonstrate by mutational analysis that GlcNAc induction is regulated primarily by the Ras1/cAMP pathway, which also regulates filamentation of C. albicans. This is perhaps not surprising given that white-opaque switching shares with filamentation several phenotypic characteristics. Finally, we show that induction by GlcNAc requires the phosphorylated master switch gene that regulates spontaneous switching, suggesting that it induces the switch from white to opaque by activating the gene product of the master switch gene. Together, our results suggest that multiple signals from bacterial co-members of the gastrointestinal tract microbiota regulate switching and, therefore, mating of C. albicans in the colonized host.

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 a...