Reduction of amphotericin resistance in stationary phase cultures of Candida albicans by treatment with enzymes.

The resistance of Candida albicans to amphotericin B methyl ester increases rapidly as cultures enter the stationary phase of growth; organisms harvested after several days in the stationary phase may have a resistance two or three orders of magnitude greater than that of exponentially growing organisms. This resistance is decreased by incubation of the organisms with enzymes which attack components of the cell wall. Of the enzymes tested, (1 leads to 3)-beta-D-glucanases are the most effective; incubation of 7 d batch cultures with exo-(1 leads to 3)-beta-D-glucanase at a concentration of 10 microgram enzyme protein (mg dry wt organisms)-1 for 24 h at 37 degrees C and pH 6.5 reduces the resistance of the organisms to a value approximating to that of exponentially growing organisms. Resistance is also decreased by treatment with chitinase, lipase, trypsin, alpha-mannosidase and (1 leads to 6)-beta-D-glucanases but, on a specific activity basis, none of these enzymes is as effective as (1 leads to 3)-beta-D-glucanase. The action of (1 leads to 3)-beta-D-glucanase is markedly enhanced by the addition during incubation of chitinase, trypsin or lipase.