title: Ferric reduction is a potential iron acquisition mechanism for Histoplasma capsulatum.
abstract: For the fungus Histoplasma capsulatum, and for other microbial pathogens, iron is an essential nutrient. Iron sequestration in response to infection is a demonstrated host defense mechanism; thus, iron acquisition may be considered an important pathogenic determinant. H. capsulatum is known to secrete 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 associated with specific iron acquisition mechanisms. The high-molecular-weight culture supernatant activity was enhanced by the addition of reduced glutathione, was proteinase K sensitive and heat labile, and could utilize ferric chloride, ferric citrate, and human holotransferrin as substrates. The low-molecular-weight culture supernatant activity was resistant to proteinase K digestion. These results are consistent with the expression by H. capsulatum of both enzymatic ferric reductase and nonproteinaceous ferric reductant, both of which are regulated by iron availability. Such components could be involved in fungal acquisition of iron from inorganic or organic ferric salts, from H. capsulatum hydroxamate siderophores, or from host Fe(III)-binding proteins, such as transferrin.
authors.affiliation: Department of Medical Microbiology and Immunology, Microbiology Doctoral Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Timmerman
authors.forename: J P
authors.initials: JP
authors.lastname: Woods
mesh_terms: D003470:Culture Media; D019286:Endopeptidase K / Q000378:metabolism; D038181:FMN Reductase; D005290:Ferric Compounds / Q000378:metabolism*; D006658:Histoplasma / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D003470:Culture Media; D005290:Ferric Compounds; D007501:Iron; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase; D019286:Endopeptidase K