Studies on the mode of antifungal action of pradimicin antibiotics. I. Lectin-mimic binding of BMY-28864 to yeast mannan in the presence of calcium.

Abstract

BMY-28864 (BMS-181184), a water-soluble pradimicin derivative, specifically bound on the yeast cell surface in the presence of calcium, which was considered to be the initial step that triggered chain reactions leading to the fungicidal action. Close cause-effect relationships of the cell wall binding of BMY-28864 with its antifungal activity and potassium leakage induction were observed by Candida albicans and Saccharomyces cerevisiae in the presence and absence of calcium. Using mannan and methyl alpha-D-mannopyranoside as specific sugars, the mode of binding of BMY-28864 to sugar was examined in vitro in the presence of calcium. Quantitative component analysis revealed that the precipitate of BMY-28864 with methyl alpha-D-mannopyranoside and calcium was a ternary complex possessing a molar component ratio of 2.1:4.3:1.0. These findings altogether proved that BMY-28864, although not protein, recognized specific sugars such as mannose in the same manner as lectin, and that the ternary complex formation of BMY-28864 with specific sugar and calcium was the first step for expression of the selective antifungal action of the pradimicin.