Candida albicans

Pathogens often face zinc restriction due to the action of nutritional immunity - host processes which restrict microbial access to key micronutrients such as zinc and iron. Candida albicans scavenges environmental zinc via two pathways. The plasma membrane transporter Zrt2 is essential for zinc uptake and growth in acidic environments. Neutralisation to pH 7 severely decreases the solubility of ionic Zn2+; this increase in pH triggers expression and activity of a second zinc scavenging system, the zincophore. This fungus-specific system consists of a secreted zinc-binding protein, Pra1, which captures zinc and returns to the cell via a syntenically expressed receptor, Zrt1. If present in excess, zinc is detoxified via a Zrc1-dependent mechanism. In C. albicans Zrc1 plays an important role in the generation of zincosomes. C. albicans faces both low and high zinc bottlenecks in vivo as Zrt2 and Zrc1 are required for kidney and liver colonisation, respectively, in a murine infection model.