FK506‐sensitive proline rotamases (FPRs), also known as FK506‐binding proteins (FKBPs), can mediate immunosuppressive drug resistance in budding yeast but their physiological roles in filamentous fungi remain opaque. Here, we report that three FPRs (cytosolic/nuclear 12.15‐kD Fpr1, membrane‐associated 14.78‐kD Fpr2 and nuclear 50.43‐kD Fpr3) are all equally essential for cellular Ca²⁺ homeostasis and contribute significantly to calcineurin activity at different levels in the insect‐pathogenic fungus Beauveria bassiana although the deletion of fpr1 alone conferred resistance to FK506. Radial growth, conidiation, conidial viability and virulence were less compromised in the absence of fpr1 or fpr2 than in the absence of fpr3, which abolished almost all growth on scant media and reduced growth moderately on rich media. The Δfpr3 mutant was more sensitive to Na⁺, K⁺, Mn²⁺, Ca²⁺, Cu²⁺, metal chelate, heat shock and UVB irradiation than was Δfpr2 while both mutants were equally sensitive to Zn²⁺, Mg²⁺, Fe²⁺, H₂O₂ and cell wall‐perturbing agents. In contrast, the Δfpr1 mutant was less sensitive to fewer stress cues. Most of 32 examined genes involved in DNA damage repair, Na⁺/K⁺ detoxification or osmotolerance and Ca²⁺ homeostasis were downregulated sharply in Δfpr2 and Δfpr3 but rarely so affected in Δfpr1, coinciding well with their phenotypic changes. These findings uncover important, but differential, roles of three FPRs in the fungal adaptation to insect host and environment and provide novel insight into their essential roles in calcium signalling pathway.

中文翻译：

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参与钙稳态的三种脯氨酸旋转酶在球孢白僵菌的胁迫耐受性、毒力和钙调磷酸酶调节中发挥不同的作用。

FK506 敏感的脯氨酸旋转异构酶 (FPRs)，也称为 FK506 结合蛋白 (FKBPs)，可以介导芽殖酵母的免疫抑制耐药性，但它们在丝状真菌中的生理作用仍然不透明。在这里，我们报告了三种 FPR（细胞溶质/核 12.15-kD Fpr1、膜相关 14.78-kD Fpr2 和核 50.43-kD Fpr3）对于细胞 Ca ²⁺稳态同样重要，并且在不同水平对钙调神经磷酸酶活性有显着贡献。昆虫病原真菌白僵菌，尽管fpr1的缺失单独赋予了对 FK506 的抗性。在没有fpr1或fpr2的情况下，径向生长、分生孢子、分生孢子活力和毒力受到的影响较小与没有fpr3的情况相比，fpr3几乎消除了稀有媒体上的所有增长，并适度减少了富媒体上的增长。Δ fpr3突变体对 Na ⁺、K ⁺、Mn ²⁺、Ca ²⁺、Cu ²⁺、金属螯合物、热休克和 UVB 照射比 Δ fpr2更敏感，而两个突变体对 Zn ²⁺、Mg 的敏感性相同²⁺、Fe ²⁺、H ₂ O ₂和细胞壁干扰剂。相比之下，Δ fpr1突变体对较少的压力线索不太敏感。32 个检测基因中的大多数参与 DNA 损伤修复，Na⁺ /K ⁺解毒或渗透压耐受性和 Ca ²⁺稳态在 Δ fpr2和 Δ fpr3 中急剧下调，但在 Δ fpr1 中很少受到如此影响，这与它们的表型变化非常吻合。这些发现揭示了三种 FPR 在真菌对昆虫宿主和环境的适应中的重要但不同的作用，并提供了对它们在钙信号通路中的重要作用的新见解。