Environmental and genetic regulation of mannan architecture in Candidozyma auris (formerly Candida auris), a comparison to other related yeast species: A review.

Abstract

Candidozyma auris (formerly Candida auris) is a globally emerging, multidrug-resistant fungal pathogen characterized by its unique ability to colonize human skin and persist on abiotic surfaces. Central to its survival and pathogenicity is the fungal cell wall, a highly dynamic structure that mediates host-pathogen interactions and immune evasion through the regulation of its outermost mannan layer. Unlike the primary model Candida albicans, C. auris possesses a denser mannan shield and structurally distinct glycans characterized by an exceptionally low molecular mass and unique phosphomannan profiles. This review consolidates current knowledge on how environmental stress conditions, including temperature, pH, carbon source, and CO2 availability, trigger substantial mannan remodeling, often leading to more compact structures that facilitate the masking of underlying immunogenic β-glucans. We examine the genetic framework of mannan biosynthesis, highlighting the roles of mannosyltransferases like OCH1 and MNT5, and signaling pathways such as HOG and PKC/CWI, which are essential for maintaining cell wall integrity and immune invisibility. Notably, substantial clade-specific structural variations were described, such as the complete absence of β-1,2-linked mannose residues in clade II isolates, which influences their relative immune recognition. Finally, we discuss how the mannan-rich extracellular matrix of biofilms fortifies C. auris resistance against antifungal agents. Elucidating these glycobiological mechanisms is critical for designing novel diagnostics, immunotherapies, and antifungal strategies to combat this persistent and immune-evasive pathogen.