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Updated: Sep 4, 2025
Author Spotlight: Exploring Cellular Zinc Regulation Through ZnT1 Functionality
Published on: June 2, 2023
Characterization and functional analysis of zinc trafficking in the human fungal pathogen Candida parapsilosis
Tamás Takács1,2, Mihály Tibor Németh1,2, Flóra Bohner1,2
1HCEMM-USZ Fungal Pathogens Research Group, Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Abstract:
The zinc restriction and zinc toxicity are part of host defence, called nutritional immunity. The crucial role of zinc homeostasis in microbial survival within a host is established, but little is known about these processes in the opportunistic human fungal pathogen Candida parapsilosis. Our in silico predictions suggested the presence of at least six potential zinc transporters (ZnTs) in C. parapsilosis-orthologues of ZRC1, ZRT3 and ZRT101-but an orthologue of PRA1 zincophore was not found. In addition, we detected a species-specific gene expansion of the novel ZnT ZRT2, as we identified three orthologue genes in the genome of C. parapsilosis. Based on predictions, we created homozygous mutant strains of the potential ZnTs and characterized them. Despite the apparent gene expansion of ZRT2 in C. parapsilosis, only CpZRT21 was essential for growth in a zinc-depleted acidic environment, in addition we found that CpZrc1 is essential for zinc detoxification and also protects the fungi against the elimination of murine macrophages. Significantly, we demonstrated that C. parapsilosis forms zincosomes in a Zrc1-independent manner and zinc detoxification is mediated by the vacuolar importer CpZrc1. Our study defines the functions of C. parapsilosis ZnTs, including a species-specific survival and zinc detoxification system.
Insights
This study reveals how Candida parapsilosis manages zinc levels for survival. It identifies key zinc transporters essential for growth and detoxification, offering insights into fungal nutritional immunity.
Area of Science:
- Microbiology
- Mycology
- Biochemistry
Background:
- Zinc homeostasis is vital for microbial survival within a host, a concept known as nutritional immunity.
- Limited information exists regarding zinc homeostasis mechanisms in the opportunistic fungal pathogen Candida parapsilosis.
Purpose of the Study:
- To investigate the roles of zinc transporters (ZnTs) in Candida parapsilosis.
- To understand zinc homeostasis, survival, and detoxification strategies in this fungal pathogen.
Main Methods:
- In silico prediction of zinc transporters in C. parapsilosis.
- Creation and characterization of homozygous mutant strains for potential ZnTs.
- Assessment of fungal growth in zinc-depleted environments and resistance to macrophage elimination.
Main Results:
- Identified six potential ZnTs, including a species-specific expansion of ZRT2 with three orthologues.
- CpZRT21 is crucial for growth in zinc-depleted acidic conditions.
- CpZrc1 is essential for zinc detoxification and protection against murine macrophage clearance.
- Candida parapsilosis forms zincosomes independently of Zrc1, with vacuolar importer CpZrc1 mediating detoxification.
Conclusions:
- Defined the functions of C. parapsilosis ZnTs.
- Uncovered a species-specific system for survival and zinc detoxification in C. parapsilosis.
- Highlighted the role of CpZrc1 in managing zinc toxicity and evading host defenses.
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