*1.2. Metal Toxicity and Resistance*

Metal toxicity occurs via the oligodynamic effect, which was initially described in 1893 in algae *Spirogyra nitida* and *Spirogyra dubia*, as toxicity or death in organisms due to exposure to trace amounts of metals, such as copper, lead, iron, or zinc [82]. In fungi, this exposure can have effects ranging interference in ergosterol biosynthesis to reduced MT activity (Table 2) [83,84].


#### **Table 2.** Mechanisms of toxicity in yeast and filamentous fungi.

In an effort to counter metal toxicity, and toxicity in general, fungi develop methods of resistance which can include the alteration of the target protein to inhibit substrate binding, cellular antimicrobial efflux, antimicrobial inactivation or degradation, restricted uptake to prevent cellular interference, overproduction of targeted proteins to prevent the complete inhibition of biochemicals, and compensation for loss of function directly related to the antimicrobial [101]. Some of these resistance mechanisms are relevant to excessive metal exposure in fungi (Table 3). Presently, research utilizes yeast such as *Saccharomyces cerevisiae* to investigate cellular and molecular impacts of fungal–metal interactions, but thorough knowledge is lacking in filamentous fungi [102–104]. Due to the increase in fungal-metal interactions, we should ensure that metal resistance mechanisms in multiple types of fungi are well-understood. In this review, we summarize existing knowledge on fungal metal homeostasis of zinc, copper, iron, manganese, and silver. Conclusions and indications are presented to pave the way for further research.

**Table 3.** Mechanisms of metal resistance in yeast and filamentous fungi.

