[Analysis of the growth system of Candida albicans in a host and the development of new antifungal material].
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 200 kDa) 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.
Watanabe
Toshihiko
T
Department of Microbiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D015195:Drug Design; D025141:Drug Resistance, Fungal; D004912:Erythrocytes / Q000378:metabolism; D005656:Fungal Proteins / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D017671:Platinum Compounds / Q000494:pharmacology*; D011485:Protein Binding
D001457:Anion Exchange Protein 1, Erythrocyte; D000935:Antifungal Agents; D005656:Fungal Proteins; D006454:Hemoglobins; D008562:Membrane Glycoproteins; D017671:Platinum Compounds; C025363:mannoproteins; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid