Pathogenic Yeast Research Group, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, Bloemfontein 9300, South Africa.
Med Mycol. 2021 Sep 3;59(9):869-881. doi: 10.1093/mmy/myab015.
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.
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.
白色念珠菌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，目前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铁还原途径在生物膜形成、PGE2 产生和秀丽隐杆线虫毒力中的作用。此外，由于白色念珠菌和铜绿假单胞菌在宿主组织中共存且涉及对宿主相关铁的竞争，我们检查了这种相互作用的影响。多铜氧化酶基因 FET99 和铁渗透酶基因 FTH1 和 FTH2 的缺失影响生物膜代谢活性，而对于 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 酶铜导入蛋白）的缺失也影响生物膜形态。对于 PGE2 的产生，FET99、FTH1、FTH2、CCC1 和 CCC2 的缺失导致单微生物生物膜的产生显著减少，而 FTH2 缺失导致多微生物生物膜的产生减少最多。FET99 和 FTH2 的 URA3 阳性突变体在秀丽隐杆线虫中的毒力减弱，可能是由于突变体无法在体内形成菌丝。因此，可以推断铁还原途径在 PGE2 合成中的作用是间接的，可能是由于其在铁稳态中的作用。
