The emergent fungal pathogen Candida auris exhibits high resistance to antifungal drugs and environmental stresses, impeding treatment and decontamination^1,2,3. The fungal factors mediating this stress tolerance are largely unknown. In the present study, we performed piggyBac, transposon-mediated, genome-wide mutagenesis and genetic screening in C. auris, and identified a mutant that grew constitutively in the filamentous form. Mapping the transposon insertion site revealed the disruption of a long non-coding RNA, named DINOR for DNA damage-inducible non-coding RNA. Deletion of DINOR caused DNA damage and an upregulation of genes involved in morphogenesis, DNA damage and DNA replication. The DNA checkpoint kinase Rad53 was hyperphosphorylated in dinorΔ mutants, and deletion of RAD53 abolished DNA damage-induced filamentation. DNA-alkylating agents, which cause similar filamentous growth, induced DINOR expression, suggesting a role for DINOR in maintaining genome integrity. Upregulation of DINOR also occurred during exposure to the antifungal drugs caspofungin and amphotericin B, macrophages, H₂O₂ and sodium dodecylsulfate, indicating that DINOR orchestrates multiple stress responses. Consistently, dinorΔ mutants displayed increased sensitivity to these stresses and were attenuated for virulence in mice. Moreover, genome-wide genetic interaction studies revealed links between the function of DINOR and TOR signalling, an evolutionarily conserved pathway that regulates the stress response. Identification of the mechanism(s) by which DINOR regulates stress responses in C. auris may provide future opportunities for the development of therapeutics.

新兴的真菌病原体耳念珠菌表现出对抗真菌药物和环境压力的高抗性，阻碍了治疗和净化^1,2,3。介导这种压力耐受性的真菌因素在很大程度上是未知的。在本研究中，我们在C. auris中进行了piggyBac、转座子介导的全基因组诱变和遗传筛选，并鉴定了一个以丝状形式组成性生长的突变体。映射转座子插入位点揭示了一个长的非编码 RNA 的破坏，命名为DINOR用于 DNA 损伤诱导的非编码 RNA。删除DINOR导致 DNA 损伤和参与形态发生、DNA 损伤和 DNA 复制的基因上调。DNA 检查点激酶 Rad53 在dinor Δ 突变体中过度磷酸化，并且RAD53的缺失消除了 DNA 损伤诱导的丝状化。引起类似丝状生长的 DNA 烷化剂诱导DINOR表达，表明DINOR在维持基因组完整性方面的作用。在暴露于抗真菌药物卡泊芬净和两性霉素 B、巨噬细胞、H ₂ O _{2和十二烷基硫酸钠期间，也发生了}DINOR的上调，表明DINOR协调了多种应激反应。始终如一，dinor Δ 突变体对这些压力表现出更高的敏感性，并且在小鼠中的毒力减弱。此外，全基因组遗传相互作用研究揭示了DINOR和 TOR 信号传导的功能之间的联系，这是一种调节应激反应的进化保守途径。识别DINOR调节耳念珠菌应激反应的机制可能为治疗学的发展提供未来的机会。