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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 \u03b2-glucan exposure and enhanced C. albicans\u2019s 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 \u03b2-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.<\/jats:p>","DOI":"10.3390\/microorganisms13030683","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:48:37Z","timestamp":1742370517000},"page":"683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cas5 Regulates the Exposure of \u03b2-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"],"prefix":"10.3390","volume":"13","author":[{"given":"Qiyue","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiye","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-8049","authenticated-orcid":false,"given":"Peipei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Pharmaceutical Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41589-022-01035-1","article-title":"Mucin O-glycans are natural inhibitors of Candida albicans pathogenicity","volume":"18","author":"Takagi","year":"2022","journal-title":"Nat. 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