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.

中文翻译：

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转录因子 Ofi1 对于白色念珠菌天然 MTLa/α 分离株的白色-不透明转换至关重要

白色念珠菌是一种机会性真菌病原体，能够在两种不同的细胞类型之间切换：白色和不透明。虽然白色到不透明的转换通常受到MTL a/α 细胞中 a1/α2 异二聚体的抑制，但最近有报道称，在某些环境条件下，一些天然MTL a/α 菌株也可能发生转换。然而， MTL a/α 细胞中控制白色不透明转换的调控程序尚不完全清楚。在这里，我们收集了 90 个白色念珠菌临床分离株，其中 16 个具有形成不透明菌落的能力。在涉及白色不透明转换的已知调节因子中，与参考菌株 SC5314 相比，只有OFI1在这 16 个菌株中表现出显着更高的表达。重要的是，即使在没有 N-乙酰氨基葡萄糖和高 CO _{2的情况下，} OFI1在临床分离株和实验室菌株中的异位表达也会促进转换频率，而高 CO 2 是MTL a/α 菌株中白色到不透明转换的最佳条件。删除OFI1会导致MTL a/α细胞中不透明形成频率和不透明细胞稳定性的降低。 Ofi1 与WOR1和WOR3的启动子结合以诱导它们的表达，从而促进白色到不透明的转换。 Ofi1 在 CTG 物种中是保守的。总之，我们的研究报告了转录因子 Ofi1 的鉴定，该转录因子是促进白色念珠菌天然MTL a/α 分离株从白色到不透明转换的关键调节因子。