For survival, pathogenic organisms such as must possess an efficient mechanism for acquiring iron in the iron-restricted environment of the human body. can use iron from a variety of sources found within the host. However, it is not clear how biologically active ferrous iron is obtained from these sources. One strategy adopted by some organisms is to reduce iron extracellularly and then specifically transport the ferrous iron into the cell. We have shown that clinical isolates of do have a cell-associated ferric-reductase activity. The determination of ferric-reductase activity of cells growing exponentially in either low- or high-iron media over a period of time indicated that reductase activity is induced when in low-iron conditions. Moreover, we have demonstrated that reductase activity is also regulated in response to the growth phase of the culture, with induction occurring upon exit from stationary phase and maximal levels being reached in early exponential stage irrespective of the iron content of the medium. These results suggest that reductase activity is regulated in a very similar manner to the ferric-reductase. Iron reduction and uptake in are closely connected to copper reduction, and possibly copper uptake. In this report we show that iron and copper reduction also appear to be linked in The ferric-reductase activity is negatively regulated by copper. Moreover, quantitative cupric-reductase assays indicated that is capable of reducing copper and that this cupric-reductase activity is negatively regulated by both iron and copper. This is the first report that has an iron- and copper-mediated ferric-reductase activity.


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