Characterization and functional analysis of zinc trafficking in the human fungal pathogen Candida parapsilosis

• Published in: Open biology Vol. 12; no. 7; p. 220077
• Main Authors: Takács, Tamás, Németh, Mihály Tibor, Bohner, Flóra, Vágvölgyi, Csaba, Jankovics, Ferenc, Wilson, Duncan, Gácser, Attila
• Format: Journal Article
• Language: English
• Published: England The Royal Society 13.07.2022
• Subjects: Animals; Candida; Candida parapsilosis - genetics; Humans; macrophage; Macrophages - microbiology; Mice; pathogen; Vacuoles; Zinc; macrophage; pathogen; zinc; Candida
• ISSN: 2046-2441; 2046-2441
• DOI: 10.1098/rsob.220077

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 Our predictions suggested the presence of at least six potential zinc transporters (ZnTs) in -orthologues of , and -but an orthologue of zincophore was not found. In addition, we detected a species-specific gene expansion of the novel ZnT as we identified three orthologue genes in the genome of . Based on predictions, we created homozygous mutant strains of the potential ZnTs and characterized them. Despite the apparent gene expansion of in , only 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 forms zincosomes in a Zrc1-independent manner and zinc detoxification is mediated by the vacuolar importer CpZrc1. Our study defines the functions of ZnTs, including a species-specific survival and zinc detoxification system.