ß (1-3)-Glucan Unmasking in C. auris for Recognition by Innate Immune Cells

Abstract

Multidrug-resistant Candida auris, a major hospital-acquired pathogen, is a severe health threat and poses a significant challenge to healthcare providers. Although there have been several studies on the anti-fungal resistance of this species, there have been very limited cell wall studies on immune responses to unmasking. C. auris cell walls are made of chitin and ß (1-3)-glucan, masked with a layer of mannosylated glycoproteins. This masking decreases the efficiency of immune detection of the ß (1-3)-glucan by innate immune cells (Dectin-1). Caspofungin belongs to the echinocandin family and has been shown to exhibit anti-fungal tendencies and reduce biofilm formation in Candida species by inhibiting the synthesis of ß (1-3)-glucan. We conducted a comparative unmasking study on nine clinical C. auris strains and one Candida albicans wild type (used as the control strain) with different caspofungin concentrations for the unmasking of ß (1-3)-glucan. Unmasking was detected by staining each cell with ß (1-3)-glucan antibodies and examining them under a fluorescent microscope. Biofilm data was also used to map the effects of caspofungin. Atomic force microscope images were used to relate cell topography to caspofungin results. Overall, our data demonstrated primary evidence suggesting that clinical strains 1099, 1100, and 1101 in Candida auris showed unmasking in the presence of sublethal caspofungin concentrations. Comparing the genotypes and phenotypes of caspofungin-sensitive strains versus resistant strains in this study could reveal new drug targets that can address resistant strains and rapid clearance of the pathogen inside the host.