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Discovery of the Diploid Form of the Emerging Fungal Pathogen Candida auris
Shuru Fan1, Chao Li1,2, Jian Bing1
1Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
Abstract:
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.
Insights
The emerging fungal pathogen Candida auris, previously thought haploid, exists in diploid forms. These diploid cells show altered growth, increased virulence, and unique gene expression, suggesting adaptive strategies.
Area of Science:
- Medical Mycology
- Molecular Biology
- Pathogen Biology
Background:
- * Candida auris is an emerging multidrug-resistant fungal pathogen first identified in 2009.
- * This human pathogen has historically been characterized as a haploid organism.
- * Its global emergence necessitates a deeper understanding of its biology and virulence factors.
Purpose of the Study:
- * To investigate the ploidy of clinical isolates of Candida auris.
- * To characterize the phenotypic and genetic differences between haploid and diploid C. auris.
- * To explore the implications of ploidy variation in C. auris pathogenesis and adaptation.
Main Methods:
- * Isolation and characterization of clinical C. auris strains.
- * Comparative analysis of growth rates and virulence in haploid and diploid cells.
- * Global gene expression profiling using transcriptomic analysis.
- * Antifungal susceptibility testing.
Main Results:
- * Discovery of diploid forms and spontaneous ploidy shifts in C. auris clinical isolates.
- * Diploid C. auris exhibits slower in vitro growth but increased virulence in a mouse model compared to haploid cells.
- * Both ploidies express distinct sets of genes involved in metabolism, cell wall maintenance, and DNA replication.
- * Antifungal susceptibility remains largely similar between haploid and diploid C. auris.
Conclusions:
- * Ploidy variation (haploid and diploid states) is a significant biological feature of Candida auris.
- * Differences in growth and virulence suggest distinct fitness advantages for each ploidy in different environments.
- * Ploidy shifts may represent an adaptive mechanism for C. auris to environmental challenges.
- * Understanding C. auris ploidy is crucial for developing effective therapeutic and control strategies.
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