PLASMA AND EXTRACELLULAR-MATRIX PROTEINS MEDIATE IN THE FATE OF CANDIDA-ALBICANS IN THE HUMAN HOST

The fungus, Candida albicans, causes trivial to life-threatening diseases in man when normal host defenses are compromised. The fungus appears to have evolved receptors (hereinafter referred to as adhesins) for human fluid phase glycoproteins such as fibronectin and immobilized basement membrane glycoproteins in order to establish and maintain a niche in the mucus-lined cavities of man. The hypothesis advanced is that the fate of the fungus may be determined by interactions with these same glycoproteins. For example, Candida may adhere to fibronectin on the surface of epithelial cells in order to maintain its residency in mucus-lined cavities, whereas when the fungus has escaped its normal niche and become bloodborne, yeast cells may be opsonized by fluid phase fibronectin and hence phagocytosed and killed more rapidly than uncoated fungi. On the other hand, bloodborne yeast cells may preferentially adhere to immobilized fibronectin exposed in the interstitial space or contained within fibrin-platelet aggregates. Adherence to immobilized proteins would enhance the ability of the fungus to establish a foothold in the human host outside its normal niche, avoid destruction by host phagocytic cells and hence establish a metastatic site of infection. This sequence of events, viz., adherence followed by growth may be similar to that which occurs in the metastasis of cancer cells. Many cancer cells employ receptors for basement membrane glycoproteins in order to effect movement from one area of the body to another. The adhesins of Candida may be analagous or perhaps homologous to the human integrin receptors. These fungal adhesins may provide the key to controlling the ability of the fungus to establish itself in areas of the body outside its normal niche. For instance, blocking adhesins with excess ligand could prohibit adherence of the fungus to immobilized glycoproteins or opsonizing the fungus with excess fluid phase liquid might reduce the ability of the fungus to adhere to the basement membrane and thence to establish a metastatic lesion.