Endocarditis due to Candida albicans has been recognized with an increasing frequency. Introduction of C. albicans into the bloodstream often results in systemic distribution of the yeast, and there may be subsequent colonization and damage to the heart, particularly if fibrin-platelet vegetations are present on the heart valves. The importance of an intact mannan molecule in the yeast cell wall for adherence to the fibrin-platelet vegetations has been demonstrated (1), and has led to speculation regarding the existence of a membrane mannose receptor which may mediate uptake of the yeast by host phagocytic cells (2). In addition, it is known that normal serum contains a soluble mannose binding protein (sMBP). This molecule, presumably synthesized by liver parenchyma, appears in two structurally related forms, a 32K soluble precursor (monomer) in serum and a 175K product (polymer) on the macrophage (3). Following endocytosis sMBP appears to be expressed in receptor form on macrophages of various mammalian species including mouse, rat, rabbit and human beings (4). The effects of this molecule on host-Candida interactions has not been ascertained, and the objectives of this study will be to determine the in vitro effects of sMBP on phagocytic cells of the host responsible for clearing C. albicans from the bloodstream, and the effect of sMBP on adherence of C. albicans to fibrin-platelet matrixes which are known to predispose to fungal endocarditis. Attempts will then be made to correlate these in vitro results with in vivo experimental models to determine the effect of sMBP on clearance of the yeast from the bloodstream of mice following intravenous challenge, and the effect of sMBP on the rate of occurrence of endocarditis in rabbits following experimental manipulation of the heart valves to elicit deposition of fibrin-platelet vegetations. Proposed polymer competition assays may provide a basis for treatment of yeast sepsis in man.
| Kitz, D J; Stahl, P D; Little, J R (1992) The effect of a mannose binding protein on macrophage interactions with Candida albicans. Cell Mol Biol 38:407-12 |
| Kitz, D J; Neuman, H R; Little, J R (1989) Clindamycin enhances murine delayed-type hypersensitivity and anti-candidal activity. J Antimicrob Chemother 23:721-8 |
