PAPULACANDIN-B - INHIBITOR OF GLUCAN SYNTHESIS IN YEAST SPHEROPLASTS

Papulacandin B, the main component of a series of antibiotics produced by the deuteromycete Papularia sphaerosperma, inhibits the growth of yeasts. It is a highly amphophilic substance containing residues of glucose, galactose and 2 long-chain unsaturated fatty acids. It does not cause the release of K+ from yeast cells and therefore differs in its mode of action from the polyene antibiotics. Papulacandin B, at concentrations slightly below the minimal inhibitory concentration, partially but selectively inhibited the incorporation of glucose into cells of Saccharomyces cerevisiae and Candida albicans. A much clearer effect was observed on spheroplasts, obtained by digestion of the yeast cell wall with snail digestive enzyme. Incubation of spheroplasts in a minimal medium stabilized by sorbitol led to the incorporation of glucose into alkali-insoluble glucan, mannan and a fraction containing mainly alkali-soluble 1,3-glucan together with some glycogen. Papulacandin B inhibited the synthesis of the alkali-insoluble fraction, while causing a slight stimulation of glucose incorporation into the other 2 polysaccharide fractions. The 50% inhibitory concentrations of papulacandin B for glucan synthesis in S. cerevisiae spheroplasts and C. albicans spheroplasts were, respectively, 0.16 .mu.g/ml and 0.03 .mu.g/ml. C. albicans cells were irradiated with UV light and selected for maximum resistance to papulacandin B. The 50% inhibitory concentration for glucan synthesis in spheroplasts prepared from this mutant was 2.5 .mu.g/ml. Echinocandin B, a polypeptide antibiotic containing a long-chain fatty acid, also inhibited the synthesis of glucan in spheroplasts. Papulacandin B and probably also echinocandin B inhibit glucan synthesis during cell-wall synthesis and thus cause lysis of cells by osmotic rupture.