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

<i>Candida albicans</i> (<i>C. albicans</i>) 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 <i>C. albicans</i> cell wall remodeling, virulence, and host interactions. Genetic manipulation and biochemical assays were used to examine the effects of Cas5 depletion on <i>C. albicans</i> 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 <i>C. albicans</i>'s ability to recruit neutrophils in vivo. Additionally, Cas5-mediated changes in cell surface hydrophobicity (CSH), CWP expressions, and morphological transition promoted <i>C. albicans</i> adhesion to biologically active surfaces (host cells) and increased fungal burden in the mouse model of OPC. In conclusion, Cas5 modulates <i>C. albicans</i> 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 <i>C. albicans</i> adhesion to host cells, as well as facilitating morphological transitions. These actions promote the colonization and invasion of <i>C. albicans</i> in OPC pathogenesis.