Fungal-Metal Interactions: A Review of Toxicity and Homeostasis

Abstract

Metal nanoparticles used as antifungals have increased the occurrence of fungal-metal interactions. However, there is a lack of knowledge about how these interactions cause genomic and physiological changes, which can produce fungal superbugs. Despite interest in these interactions, there is limited understanding of resistance mechanisms in most fungi studied until now. We highlight the current knowledge of fungal homeostasis of zinc, copper, iron, manganese, and silver to comprehensively examine associated mechanisms of resistance. Such mechanisms have been widely studied in Saccharomyces cerevisiae, but limited reports exist in filamentous fungi, though they are frequently the subject of nanoparticle biosynthesis and targets of antifungal metals. In most cases, microarray analyses uncovered resistance mechanisms as a response to metal exposure. In yeast, metal resistance is mainly due to the down-regulation of metal ion importers, utilization of metallothionein and metallothionein-like structures, and ion sequestration to the vacuole. In contrast, metal resistance in filamentous fungi heavily relies upon cellular ion export. However, there are instances of resistance that utilized vacuole sequestration, ion metallothionein, and chelator binding, deleting a metal ion importer, and ion storage in hyphal cell walls. In general, resistance to zinc, copper, iron, and manganese is extensively reported in yeast and partially known in filamentous fungi; and silver resistance lacks comprehensive understanding in both.

Keywords: fungal–metal interaction; homeostasis; nanoparticles; resistance; toxicity.

Figure 1

S. cerevisiae zinc homeostatic systems.

Figure 2

Yeast copper transport systems. In S. cerevisiae, cupric reductase, Fre1 reduces extracellular cupric oxide for transport across high and low-affinity copper membrane transports Ctr1 and Fet4. From the cytoplasm, Ccc2 shuttles Cu⁺ to Golgi bodies, and Pic2 shuttles Cu⁺ to the mitochondrial matrix. During meiosis in S. pombe, Mfc1 transports Cu⁺ across the forespore membrane.

Figure 3

Mn²⁺ uptake and detoxification systems in S. cerevisiae.