Candidaalbicans の宿主生体内増殖機構の解析と新規抗菌物質の開発

抄録

Hyphal cells of Candida albicans bind to human hemoglobin, but not yeast cells. The amount of hemoglobin receptor is significantly higher in hyphal cells than on yeast cells. Only the hyphal cells of C. albicans use hemoglobin as a source of iron. The culture supernatant of C. albicans promoted the disruption of human red blood cells (RBC). Hemolytic activity was detected in a sugar-rich fraction (about 200kDa) purified by Sephacryl S-100 chromatography. As the hemolytic activity was adsorbed by concanavalin A (Con A)-Sepharose, the hemolytic factor might be a mannoprotein. The activity was inactivated by periodate oxidation, indicating that the sugar moiety of the mannoprotein plays an important role in hemolysis. The structure of the sugar moiety of the mannoprotein was identified as a cell wall mannan by ¹H-NMR analysis, and purified C. albicans mannan promoted the disruption of RBC. The binding of mannan to RBC was demonstrated by flow cytometric analysis and was inhibited by the addition of the band 3 protein inhibitor, 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS). The hemolysis caused by mannan is inhibited by DIDS, 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid, and Bis (sulfosuccinimidyl) suberate, but not by pyridoxal-5′-phosphate. A new platinum derivative of the form H[Pt(IV) (Hdigly)Cl₂(OH)₂] (Hdigly=glycylglycine) has candidacidal activity 10-fold lower than that of cisplatin.