The transcription factor Ofi1 is critical for white‐opaque switching in natural MTLa/α isolates of Candida albicans

• Published in: Molecular microbiology 2024-02, Vol.121 (2), p.275-290
• Main Authors: Cui, Hao, Yang, Dandan, Gong, Shengwei, Zhang, Yaling, Dong, Bin, Su, Chang, Yang, Lianjuan, Lu, Yang
• Format: Article
• Language: English
• Subjects: Candida albicans; Candida albicans - genetics; Candida albicans - metabolism; Carbon dioxide; Clinical isolates; Ectopic expression; Environmental conditions; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal; MTLa/α; N-Acetylglucosamine; OFI1; Opportunist infection; Phenotype; Promoter Regions, Genetic - genetics; Switching; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; white‐opaque switching; WOR1
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.15222

Candida albicans, an opportunistic fungal pathogen, is able to switch between two distinct cell types: white and opaque. While white‐to‐opaque switching is typically repressed by the a1/α2 heterodimer in MTLa/α cells, it was recently reported that switching can also occur in some natural MTLa/α strains under certain environmental conditions. However, the regulatory program governing white‐opaque switching in MTLa/α cells is not fully understood. Here, we collected 90 clinical isolates of C. albicans, 16 of which possess the ability to form opaque colonies. Among the known regulators implicated in white‐opaque switching, only OFI1 exhibited significantly higher expression in these 16 strains compared to the reference strain SC5314. Importantly, ectopic expression of OFI1 in both clinical isolates and laboratory strains promoted switching frequency even in the absence of N‐acetylglucosamine and high CO2, the optimal condition for white‐to‐opaque switching in MTLa/α strains. Deleting OFI1 resulted in a reduction in opaque‐formation frequency and the stability of the opaque cell in MTLa/α cells. Ofi1 binds to the promoters of WOR1 and WOR3 to induce their expression, which facilitates white‐to‐opaque switching. Ofi1 is conserved across the CTG species. Altogether, our study reported the identification of a transcription factor Ofi1 as the critical regulator that promotes white‐to‐opaque switching in natural MTLa/α isolates of C. albicans. In this study, we investigated the white‐opaque switching phenomenon in Candida albicans, an opportunistic fungal pathogen. While white‐opaque switching is traditionally repressed by the a1/α2 heterodimer, our research focused on clinical isolates, revealing that among known regulators, only OFI1 exhibited significantly higher expression in strains with opaque colony‐forming ability. OFI1 overexpression promoted switching frequency, even in suboptimal conditions, highlighting Ofi1 as a critical transcription factor governing white‐opaque switching in natural MTLa/α isolates of C. albicans.