Dataset for: Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in Candida albicans

Fungal pathogens like Candida albicans exhibit several survival mechanisms to evade attack by antifungals and colonize host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain (7TMD) topology, similar to the G-protein-coupled receptors (GPCR) and is unique to the fungal kingdom. Our findings point towards a role for plasma membrane localized Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility, the rta3Δ/Δ strain displays increased inward translocation (flip) of fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane attributed to enhanced PC-specific flippase activity. We also assign a novel role to Rta3 in the Bcr1- regulated pathway during in vivo biofilm development. Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target genes involved in cell surface properties, adhesion, and hyphal growth. We show that the rta3Δ/Δ mutant is biofilm-defective in a rat venous catheter model of infection and that BCR1 overexpression rescues this defect, indicating that Bcr1 functions downstream of Rta3 to mediate biofilm formation in C. albicans. The identification of this novel Rta3-dependent regulatory network that governs biofilm formation and PC asymmetry across the plasma membrane will provide important insights into C. albicans pathogenesis by providing insight into how C. albicans adapts to the host environment.

像白念珠菌（Candida albicans）这类真菌病原体，拥有多种生存策略以逃逸抗真菌药物的攻击并定植于宿主组织。Rta3作为Rta1样脂质转运外排蛋白家族成员，具有7跨膜结构域（7-transmembrane domain, 7TMD）拓扑结构，与G蛋白偶联受体（G-protein-coupled receptors, GPCR）类似，且为真菌界所特有。本研究结果表明，定位于质膜的Rta3可通过维持线粒体能量代谢，使真菌对烷基磷酸胆碱（alkylphosphocholine）类似物米替福新（miltefosine）产生耐受性。与米替福新敏感性升高表型一致，rta3Δ/Δ缺失株的质膜对荧光基团标记的磷脂酰胆碱（phosphatidylcholine, PC）的内转运（翻转，flip）活性增强，这归因于特异性磷脂酰胆碱翻转酶活性的提升。本研究还揭示了Rta3在体内生物膜发育过程中Bcr1调控通路中的全新功能。转录组分析显示，Rta3可调控与细胞表面特性、黏附及菌丝生长相关的Bcr1靶基因的表达。研究证实，rta3Δ/Δ突变株在大鼠静脉导管感染模型中表现出生物膜形成缺陷，而过表达BCR1可挽救该缺陷，这表明Bcr1在Rta3下游发挥功能，介导白念珠菌的生物膜形成。本研究鉴定出这一依赖于Rta3的新型调控网络，其可调控生物膜形成及质膜上磷脂酰胆碱的不对称分布，通过解析白念珠菌适应宿主环境的机制，为阐明白念珠菌的致病机理提供重要见解。