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 two long-chain unsaturated fatty acids. It does not cause the release of potassium ions 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 stabilised 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 two polysaccharide fractions. The 50 % inhibitory concentrations of papulacandin B for glucan synthesis in S. cerevisiae spheroplasts and C. albicans spheroplasts were respectively 0.16 pg/ml and 0.03 pg/ml. C. albicans cells were irradiated with ultraviolet 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 pg/ml. Echinocandin B, a polypeptide antibiotic containing a long-chain fatty acid, also inhibited the synthesis of glucan in spheroplasts. It is concluded that papulacandin B and probably also echinocandin B inhibit glucan synthesis during cell-wall synthesis, and thus cause lysis of cells by osmotic rupture.
Sorangicin A, a macrolide polyether antibiotic and the ansamycin antibiotic rifampicin inhibit DNA-dependentRNApolymerase to a similar extent. Resistance to sorangicin A is due to a mutation in the RNApolymerase which renders the enzyme less sensitive. Parallel investigations with rifampicin revealed partial cross-resistance, which was more marked in sorangicin A-resistant mutants than in rifampicin-resistant mutants. Sorangicin A is a new type of macrolide polyether antibiotic isolated from the gliding bacterium Sorangium cellulosum. Its antimicrobial properties are similar to those of the ansamycin antibiotic rifampicin. Sorangicin A is highly active against Gram-positive bacteria (MIC<0.01~2^g/ml) and less so against Gram-negative bacteria (MIC 2~>32^g/ml). The drug also resembles rifampicin in its mechanism of action, since it specifically affects bacterial DNA-dependent RNApolymerase1~3). The chemical structures of the two drugs are, however, quite different. The aim of the present work was to analyze the mechanismof resistance of Escherichia coli to sorangicin A and to compare it to the resistance against rifampicin.
Papulacandin B inhibits glucan biosynthesis in cells of Saccharomyces cerevisiae and Candida albicans. Biological studies with a series of papulacandin derivatives showed that the short fatty acid chain and the galactose residue are not required for activity at the target site, but that they can affect penetration. On the other hand, the long fatty acid residue is essential for biological activity.
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