Filamentation in Candida auris, an emerging fungal pathogen of humans: passage through the mammalian body induces a heritable phenotypic switch

Huizhen Yue,Jian Bing,Qiushi Zheng,Yulong Zhang,Tianren Hu,Han Du,Hui Wang,Guanghua Huang

doi:10.1038/s41426-018-0187-x

Abstract

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.

Highlights

Phenotypic plasticity is a common strategy used by microbial pathogens to adapt to diverse host environments[1–4]
Our results suggest that passage through a mammalian body can potentially erase the cellular memory of filamentation and promote the switch to a typical yeast phenotype
Our results reveal that the ability to switch between the typical yeast and filamentous forms is heritable and triggered by passage through the animal (Fig. 4c), whereas the switch between FC yeast and the filamentous form is nonheritable and temperature -dependent (Fig. 4d)

Summary

Introduction

Phenotypic plasticity is a common strategy used by microbial pathogens to adapt to diverse host environments[1–4]. In C. albicans, the switch between the normal yeast state and the filamentous form has been well-documented as a response to environmental changes[9,10]. Several hostrelated factors, such as physiological temperature (37 °C), neutral pH, elevated CO2 levels, and serum presence, act. Filamentous C. albicans cells quickly switch back to the normal yeast form when the inducing factors are removed from the culture conditions. The white and opaque phenotypes are heritable and epigenetically regulated; the switching frequencies are affected by environmental factors[11–14]. Both white and opaque cells can heritably maintain their cellular phenotypes for multiple generations

Methods

Results

Conclusion