The action of 2-deoxy-D-glucose on the incorporation of glucose into (1----3)-beta-glucan in stationary phase cultures of Candida albicans.

Abstract

2-Deoxy-D-glucose added to cultures of Candida albicans in the stationary phase of growth inhibited the incorporation of glucose into the (1----3)-beta-glucan fraction of the organisms. In the presence of ATP and cell extracts it was converted to 2-deoxy-D-glucose phosphate and when UTP was also present, material with the electrophoretic properties of UDP-2-deoxy-D-glucose was formed. In similar conditions glucose formed glucose phosphates, UDP-glucose and other products. Evidence was obtained that the analogue, after conversion to a phosphate derivative, was an inhibitor of phosphoglucomutase. When C. albicans was grown in the presence of 2-deoxy-D-glucose for 24 h, analogue residues became incorporated into the (1----3)-beta-glucan fraction and the subsequent rate of incorporation of glucose into that fraction was enhanced. The rate of turnover of glucose in this beta-glucan fraction was greater than in controls. Pretreatment of cultures with beta-glucanase, or incubation under conditions known to stimulate endogenous beta-glucanases, increased the subsequent rate of glucose incorporation and this increase was enhanced by growth in the presence of 2-deoxy-D-glucose. The analogue thus had the effect of altering the stability and glucose-acceptor function of (1----3)-beta-glucan chains. This could affect the properties of the polymer network leading to the known effect of the analogue in delaying the onset of phenotypic resistance to amphotericin methyl ester in stationary phase cultures of C. albicans.