Fungal zinc metabolism and its connections to virulence

Abstract

Zinc is a ubiquitous metal in all life forms, as it is a structural component of the almost 10% of eukaryotic proteins, which are called zinc-binding proteins. In zinc-limiting conditions such as those found during infection, pathogenic fungi activate the expression of several systems to enhance the uptake of zinc. These systems include ZIP transporters (solute carrier 39 family) and secreted zincophores, which are proteins that are able to chelate zinc. The expression of some fungal zinc uptake systems are regulated by a master regulator (Zap1), first characterized in the yeast Saccharomyces cerevisiae. In this review, we highlight features of zinc uptake and metabolism in human fungal pathogens and aspects of the relationship between proper zinc metabolism and the expression of virulence factors and adaptation to the host habitat.

Keywords: ZAP transcription factor; fungal virulence; zinc ZIP transporters; zinc deprivation; zinc metabolism.

Figure 1

Zinc-binding proteins associated biological processes in fungi. (A) The number of zinc finger transcription factors and zinc-binding proteins compared to the total proteome from fungi. The predicted proteomes of A. fumigatus, C. albicans, C. neoformans, C. gattii, and S. cerevisiae were retrieved from their respective genome assemblies in NCBI (Accession numbers GCA_000002655.1, GCA_000182965.2, GCA_000149245.2, GCA_000185945.1, GCA_000146045.2, respectively). The protein sequences were submitted to the UFO webserver (Meinicke, 2009) for functional profiling. All proteins with the Gene Ontology annotation “zinc ion binding” (GO:0008270) were considered to be zinc-binding proteins. (B) The 311 yeast proteins annotated as zinc-binding proteins in the Yeast Genome Database were submitted to GO-slim analysis (Cherry et al., 2012). The 10 most abundant biological process (left graph) and molecular function (right graph) associations were considered, and the fraction of proteins in each class is depicted.