Fungal infections continue to represent a major threat to public health, particularly with the emergence of multidrug-resistant fungal pathogens. As part of the innate immune response, the host modulates the availability of metals as armament against pathogenic microbes, including fungi. The transition metals Fe, Cu, Zn, and Mn are essential micronutrients for all life forms, but when present in excess, these same metals are potent toxins. The host exploits the double-edged sword of these metals, and will either withhold metal micronutrients from pathogenic fungi or attack them with toxic doses. In response to these attacks, fungal pathogens cleverly adapt by modulating metal transport, metal storage, and usage of metals as cofactors for enzymes. Here we review the current state of understanding on Fe, Cu, Zn, and Mn at the host–fungal pathogen battleground and provide perspectives for future research, including a hope for new antifungals based on metals.


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