Paracoccidioides spp. ferrous and ferric iron assimilation pathways

Area of Science:

• Mycology
• Molecular Biology
• Biochemistry

Background:

• Iron is vital for fungal growth and survival.
• Fungi typically acquire iron via siderophores or reductive iron assimilation (RIA).
• Paracoccidioides spp. lack a canonical Ftr1 iron permease homolog.

Purpose of the Study:

• Investigate iron uptake mechanisms in Paracoccidioides spp.
• Characterize the role of zinc-regulated transporter homologs (Zrts) in iron assimilation.
• Identify potential drug targets for inhibiting fungal proliferation.

Main Methods:

• 2,3,5-triphenyltetrazolium chloride (TTC)-overlay assay to detect ferric reductase activity.
• (59)Fe uptake assays to measure iron assimilation.
• RNA sequencing (RNAseq) and quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression under iron-deprived conditions.

Main Results:

• Both Paracoccidioides Pb01 and Pb18 strains exhibit ferric reductase activity.
• Only Pb18 demonstrates reductase-dependent iron uptake.
• Zrts are upregulated in iron-deprived conditions, suggesting a role in iron acquisition.
• Siderophore uptake and biosynthesis genes are also upregulated under iron limitation.

Conclusions:

• Paracoccidioides spp. likely utilize a non-classical RIA pathway involving ferric reductases and ZIP transporters (Zrts).
• The fungus also employs siderophore-mediated iron uptake pathways.
• These iron metabolism pathways and associated surface molecules represent potential targets for antifungal drug development.