Candida albicans is a pathogenic yeast that causes a variety of primary and secondary infections in man and animals. These infections can be manifested in cutaneous and mucocutaneous tissues, and nearly any major body organ. Recently, candidosis has been recognized as a serious mycotic complication of the Acquired Immune Deficiency Syndrome (AIDS). Very little is known concerning the pathogenesis of C. albicans. Factors, like toxin production, enzymology, dimorphic transformations, have all been incriminated in the pathogenesis of this yeast. Some thirty-years ago, it was shown that serum was fungicidal. Later, it was found that the inhibitory properties of serum were related to the degree of iron saturation of transferrin. Since then, other host iron-binding proteins have been found to inhibit fungal growth. Because iron is required for fungal survival, these iron-binding proteins may limit fungal replication by iron starvation. Recent studies have shown that Candida albicans in response to iron starvation secretes low molecular weight siderophores which function to scavenge iron and return it to the yeast in a utilizable form. The hypothesis of this proposal addresses the importance of candidal siderophores for both the in vitro and in vivo survival of the yeast. The proposal will a.) chemically characterize the siderophores. b.) determine if the siderophore can scavenge iron from host iron-binding proteins to support fungal growth, and c.) characterize the mechanism by which siderophores mediate iron transport into the cell. These studies should contribute fundamental knowledge to our understanding of the basic mechanisms of pathogenesis, and may provide an insight as to a means of interrupting the fungal growth cycle.
