Cas5 Regulates the Exposure of β-Glucan, the Cell Surface Hydrophobicity, and the Expression of Cell Wall Proteins to Remodel the Candida albicans Cell Wall and Participates in the Recruitment of Neutrophils.

Abstract

Candida albicans (C. albicans) is a major opportunistic fungal pathogen that causes life-threatening infections, particularly in immunocompromised individuals, underscoring the critical need to understand its pathogenic mechanisms. This study investigates the role of Cas5, a key transcription factor, in regulating C. albicans cell wall remodeling, virulence, and host interactions. Genetic manipulation and biochemical assays were used to examine the effects of Cas5 depletion on C. albicans cell wall structure, adhesion to host cells, morphology transition, innate immune cells recruitment, and pathogenicity in a BALB/C mouse model of oropharyngeal candidiasis (OPC). The results showed that the Cas5 depletion mediated β-glucan exposure and enhanced C. albicans's ability to recruit neutrophils in vivo. Additionally, Cas5-mediated changes in cell surface hydrophobicity (CSH), CWP expressions, and morphological transition promoted C. albicans adhesion to biologically active surfaces (host cells) and increased fungal burden in the mouse model of OPC. In conclusion, Cas5 modulates C. albicans cell wall remodeling by masking cell wall β-glucan, altering CSH, and regulating the expression of cell wall proteins (CWPs). Additionally, Cas5 participates in inhibiting neutrophil recruitment and enhancing the C. albicans adhesion to host cells, as well as facilitating morphological transitions. These actions promote the colonization and invasion of C. albicans in OPC pathogenesis.