Identification and characterization of the candida albicans iron ferroxidase genes reveals novel partnerships with iron permeases for high-affinity iron uptake

Abstract

High-affinity iron transporters in fungi are two-component systems consisting of a specific pair of multicopper ferroxidase and iron permease. An organism may contain two such transporters, one localizing to the plasma membrane for iron uptake and the other at the vacuolar membrane for vacuole-cytosol iron transport. The pathogenic fungus Candida albicans possesses five multicopper ferroxidases and three iron permeases. Here, we have investigated the regulation and functions of the ferroxidase genes and their partnerships with the permeases. FET3, FET34 and FET99 were observed to be the only ferroxidases that exhibited elevated transcription in low-iron conditions. Co-localisation studies suggested Ftr1p/Fet34p and Fth1p/Fet3p partnerships. Interestingly, Fet99p appeared to be able to partner Ftr1p in the absence of Fet34p. This was supported by the loss of iron-uptake only upon deletion of FET34 and FET99. This alternate partnership for the high-affinity iron uptake might be beneficial for C. albicans survival and virulence.