Components of the iron reductive pathway of Candida albicans have been implicated in the production of prostaglandin E2 (PGE2) and virulence. However, it is unknown whether other components of this pathway influence PGE2. We investigated the role of the iron reductive pathway of C. albicans in biofilm formation, PGE2 production, and virulence in Caenorhabditis elegans. Additionally, as the co-occurrence of C. albicans and Pseudomonas aeruginosa in host tissues is frequent and involves competition for host-associated iron, we examined the effects of this interaction. Deletion of multicopper oxidase gene, FET99, and iron permease genes, FTH1 and FTH2, affected biofilm metabolic activity, and for the FTH2 mutant, also biofilm morphology. Deletion of CCC1 (vacuolar iron transporter) and CCC2 (P-type ATPase copper importer) also influenced biofilm morphology. For PGE2 production, deletion of FET99, FTH1, FTH2, CCC1, and CCC2 caused a significant reduction by monomicrobial biofilms, while FTH2deletion caused the highest reduction in polymicrobial biofilms. URA3 positive mutants of FET99 and FTH2 demonstrated attenuated virulence in C. elegans, potentially due to the inability of mutants to form hyphae in vivo. Deductively, the role of the iron reductive pathway in PGE2 synthesis is indirect, possibly due to their role in iron homeostasis. Lay Summary Iron uptake is vital for disease-causing microbes like Candida albicans. Using strains deficient in some iron-uptake genes, we show that iron-uptake genes, especially FET99 and FTH2, play a role in biofilm formation, prostaglandin production, and virulence in the nematode infection model.

中文翻译：

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白色念珠菌高亲和力还原铁获取途径在前列腺素 E2 产生、毒力和与铜绿假单胞菌相互作用中的作用

白色念珠菌的铁还原途径的成分与前列腺素 E2 (PGE2) 的产生和毒力有关。然而，尚不清楚该途径的其他成分是否会影响 PGE2。我们研究了白色念珠菌的铁还原途径在秀丽隐杆线虫生物膜形成、PGE2 产生和毒力中的作用。此外，由于白色念珠菌和铜绿假单胞菌在宿主组织中的共同发生是频繁的并且涉及与宿主相关的铁的竞争，我们检查了这种相互作用的影响。多铜氧化酶基因 FET99 和铁通透酶基因 FTH1 和 FTH2 的缺失影响生物膜代谢活性，对于 FTH2 突变体，也影响生物膜形态。CCC1（液泡铁转运蛋白）和CCC2（P型ATP酶铜进口蛋白）的缺失也影响了生物膜的形态。对于 PGE2 生产，FET99、FTH1、FTH2、CCC1 和 CCC2 的缺失导致单微生物生物膜的显着减少，而 FTH2 的缺失导致多微生物生物膜的最大减少。FET99 和 FTH2 的 URA3 阳性突变体在秀丽隐杆线虫中表现出减弱的毒力，这可能是由于突变体无法在体内形成菌丝。推断地，铁还原途径在 PGE2 合成中的作用是间接的，可能是由于它们在铁稳态中的作用。总结 铁的吸收对于像白色念珠菌这样的致病微生物至关重要。使用缺乏某些铁摄取基因的菌株，我们证明铁摄取基因，特别是 FET99 和 FTH2，在生物膜形成中发挥作用，