Paracoccidioides spp. ferrous and ferric iron assimilation pathways

Abstract

Iron is an essential micronutrient for almost all organisms, including fungi. Usually, fungi can uptake iron through receptor-mediated internalization of a siderophore or heme, and/or reductive iron assimilation (RIA). Traditionally, the RIA pathway consists of ferric reductases (Fres), ferroxidase (Fet3) and a high-affinity iron permease (Ftr1). Paracoccidioides spp. genomes do not present an Ftr1 homolog. However, this fungus expresses zinc regulated transporter homologs (Zrts), members of the ZIP family of membrane transporters that are able in some organisms to transport zinc and iron. A 2,3,5-triphenyltetrazolium chloride (TTC)-overlay assay indicates that both Pb01 and Pb18 express a ferric reductase activity; however, 59Fe uptake assays indicate that only in Pb18 is this activity coupled to a reductase-dependent iron uptake pathway. In addition, Zrts are up-regulated in iron deprivation, as indicated by RNAseq and qRT-PCR using Pb01 transcripts. RNAseq strategy also demonstrated that transcripts related to siderophore uptake and biosynthesis are up-regulated in iron-deprived condition. The data suggest that the fungus could use both a non-classical RIA, comprising ferric reductases and Fe/Zn permeases (Zrts), and siderophore uptake pathways under iron-limited conditions. The study of iron metabolism reveals novel surface molecules that could function as accessible targets for drugs to block iron uptake and, consequently, inhibit pathogen's proliferation.

Defects in the Ferroxidase That Participates in the Reductive Iron Assimilation System Results in Hypervirulence in Botrytis Cinerea

“…Finally, recent investigations have provided additional perspectives for RIA. In Paracoccidioides species, whose genome does not encode an FTR1 iron permease, the authors suggested that the fungus utilizes a nonclassical FTR1-independent RIA system that requires Fe/Zn permeases, known as Zrts, that may account for iron uptake (68), adding an additional layer of complexity.…”

In vitro inhibition of Saccharomyces cerevisiae growth by Metschnikowia spp. triggered by fast removal of iron via two ways

“…1a, b) described more in detail in our previous publication [35]. Microorganisms can assimilate iron through receptormediated internalization of a water soluble siderophore (low molecular weight ferric ion-specific chelator) or heme and/or reductive iron assimilation [38,39]. To the best of our knowledge, the mechanism of iron uptake by Metschnikowia yeasts is not elucidated yet.…”

Multicopper Oxidases in Saccharomyces cerevisiae and Human Pathogenic Fungi

“…For instance, the presence of iron for the human pathogenic Paracoccidioides species also influences virulence, although no detailed study is available about the MCOs of this particular fungus. Only in silico analyses suggest that PAAG_06004 and PADG_05994 could encode functional ferroxidases [90]. Laccases also play an important role in fungal pathogens by generating mainly melanin.…”