The roles of zinc and copper sensing in fungal pathogenesis

All organisms must secure essential trace nutrients, including iron, zinc, manganese and copper for survival and proliferation. However, these very nutrients are also highly toxic if present at elevated levels. Mammalian immunity has harnessed both the essentiality and toxicity of micronutrients to defend against microbial invasion — processes known collectively as ‘nutritional immunity’. Therefore, pathogenic microbes must possess highly effective micronutrient assimilation and detoxification mechanisms to survive and proliferate within the infected host. In this review we compare and contrast the micronutrient homeostatic mechanisms of Cryptococcus and Candida — yeasts which, despite ancient evolutionary divergence, account for over a million life-threatening infections per year. We focus on two emerging arenas within the host–pathogen battle for essential trace metals: adaptive responses to zinc limitation and copper availability.