Ferric reduction is a potential iron acquisition mechanism for Histoplasmacapsulatum

For the fungus Histoplasma capsulatum, and for other microbial pathogens, i ron is an essential nutrient, Iron sequestration in response to infection i s a demonstrated host defense mechanism; thus, iron acquisition may be cons idered an important pathogenic determinant. H, capsulatum is known to secre te Fe(III)-binding hydroxamate siderophores, which is one common microbial process for acquiring iron, Here, we report H, capsulatum ferric reduction activities in whole yeast cells and in both high- and low-molecular-weight fractions of culture supernatants. Each of these activities was induced or derepressed by growth under iron-limiting conditions, a phenomenon often as sociated with specific iron acquisition mechanisms, The high-molecular-weig ht culture supernatant activity was enhanced by the addition of reduced glu tathione, was proteinase It sensitive and heat labile, and could utilize fe rric chloride, ferric citrate, and human holotransferrin as substrates, The low-molecular weight culture supernatant activity was resistant to protein ase K digestion. These results are consistent with the expression by H. cap sulatum of both enzymatic ferric reductase and nonproteinaceous ferric redu ctant, both of which are regulated by iron availability. Such components co uld be involved in fungal acquisition of iron from inorganic or organic fer ric salts, from H. capsulatum hydroxamate siderophores, or from host Fe(III ) binding proteins, such as transferrin.