The role of zinc in the pathogenicity of human fungal pathogens.

Fungal pathogens now account for an unprecedented burden on human health. Like all microorganisms, these fungi must successfully forage for essential micronutrients such as zinc in order to proliferate. However, pathogenic microbes face an additional hurdle in securing zinc from their environment: the action of host nutritional immunity which strictly manipulates microbial access to this essential, but also potentially toxic trace metal. This review introduces the relevant pathogenic species and goes on to cover the molecular mechanisms of zinc uptake by human fungal pathogens. Fungi scavenge zinc from their environment via two basic mechanisms: via a family of cellular zinc importers-the ZIP transporters; and via a unique secreted zinc binding protein-the zincophore. However the genetic requirement of these systems for fungal virulence is highly species-specific. As well as zinc scarcity, potential intoxification with this heavy metal can occur and, unlike bacteria, fungi deal with environmental insult this via intraorganellar compartmentalization. Zinc availability also modulates the morphogenic behavior of a subset of pathogenic yeast species. This chapter will cover these different aspects of zinc availability on the physiology of human fungal pathogens with emphasis on the major pathogenic species Candida albicans.