White-Brown switching controls phenotypic plasticity and virulence of Candida auris
Trinh Phan-Canh,
Sabrina Jenull,
Tamires Bitencourt,
Saskia Seiser,
Doris Moser,
Marjan Motamedi,
Anuradha Chowdhary,
Adelheid Elbe-Bürger,
Karl Kuchler
Affiliations
Trinh Phan-Canh
Max Perutz Labs Vienna, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9/2, 1030 Vienna, Austria; Medical University of Vienna, Department of Dermatology, Währinger Gürtel 18-20, 1090 Vienna, Austria
Sabrina Jenull
Max Perutz Labs Vienna, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9/2, 1030 Vienna, Austria
Tamires Bitencourt
Max Perutz Labs Vienna, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Institute for Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria
Saskia Seiser
Medical University of Vienna, Department of Dermatology, Währinger Gürtel 18-20, 1090 Vienna, Austria
Doris Moser
Department of Oral and Maxillofacial Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Marjan Motamedi
Max Perutz Labs Vienna, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9/2, 1030 Vienna, Austria; Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Anuradha Chowdhary
Medical Mycology Unit, Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India; National Reference Laboratory for Antimicrobial Resistance in Fungal Pathogens, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
Adelheid Elbe-Bürger
Medical University of Vienna, Department of Dermatology, Währinger Gürtel 18-20, 1090 Vienna, Austria
Karl Kuchler
Max Perutz Labs Vienna, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Dr.-Bohr-Gasse 9/2, 1030 Vienna, Austria; Corresponding author
Summary: The skin-tropic human fungal pathogen Candida auris can cause life-threatening infections of high mortality in healthcare settings. Clinical isolates display a pronounced heterogeneity in virulence traits, such as antifungal susceptibility, stress adaptation, and growth fitness. However, the mechanistic bases underlying intraspecies variations remain enigmatic. Here, we show that C. auris cell populations encompass multiple cell states that allow for reversible morphogenetic switching at high frequency, resulting in distinct White and Brown morphotypes. Further, we demonstrate that temperature and carbon source are key drivers of morphogenesis. White and Brown morphotypes show distinct phenotypes concerning stress tolerance, antifungal susceptibility, and fitness on murine skin. Our data reveal that morphogenesis engages both transcriptional activators, including Wor1, Msn4, Crz2, and Rca1, and the Efg1 repressor. Importantly, the stochastic conversion explains the extreme plasticity underlying adaptive virulence traits. The results allow for the exploration of the therapeutic potential of morphogenesis regulators in C. auris.
