CANDIDA-ALBICANS HAS A CELL-ASSOCIATED FERRIC-REDUCTASE ACTIVITY WHICH IS REGULATED IN RESPONSE TO LEVELS OF IRON AND COPPER

For survival, pathogenic organisms such as Candida albicans must posse ss an efficient mechanism for acquiring iron in the iron-restricted en vironment of the human body. C. albicans can use iron from a variety o f sources found within the host. However, it is not clear how biologic ally active ferrous iron is obtained from these sources. One strategy adopted by some organisms is to reduce iron extracellularly and then s pecifically transport the ferrous iron into the cell. We have shown th at clinical isolates of C. albicans do have a cell-associated ferric-r eductase activity. The determination of ferric-reductase activity of c ells growing exponentially in either low- or high-iron media over a pe riod of time indicated that C. albicans reductase activity is induced when in low-iron conditions. Moreover, we have demonstrated that C. al bicans reductase activity is also regulated in response to the growth phase of the culture, with induction occurring upon exit from stationa ry phase and maximal levels being reached in early exponential stage i rrespective of the iron content of the medium. These results suggest t hat C. albicans reductase activity is regulated in a very similar mann er to the Saccharomyces cerevisiae ferric-reductase. Iron reduction an d uptake in S. cerevisiae are closely connected to copper reduction, a nd possibly copper uptake. In this report we show that iron and copper reduction also appear to be linked in C. albicans. The ferric-reducta se activity is negatively regulated by copper. Moreover, quantitative cupric-reductase assays indicated that C. albicans is capable of reduc ing copper and that this cupric-reductase activity is negatively regul ated by both iron and copper. This is the first report that C. albican s has an iron- and copper-mediated ferric-reductase activity.