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.

Papulacandin, a new antibiotic complex, active against Candida albicans and several other yeasts, was isolated from a strain of Papularia sphaerosperma. The fermentation, isolation, physico-chemical properties and biological activity of the five structurally related papulacandins A, B, C, D and E are reported. Papulacandin B, the main component, was assigned the formula of C"HO,O,,.

Duramycins B and C, two new lanthionine containing antibiotics, have been isolated from Streptoverticillium strain R2075 and Streptomyces griseoluteus (R2107). The known antibiotics duramycin and cinnamycin were reisolated from Streptoverticillium hachijoense (DSM401 14) and Streptomyces longisporoflavus (DSM40165). The structures of these latter two compoundsshould be revised by changing amino acid residue 3 to glutamine and 17 to asparagine, respectively.Cinnamycin therefore seems to be identical to Ro 09-0198. Leucopeptin has been shown to be identical to duramycin. Physico-chemical data of these compounds provide evidence for a similar structure for all duramycin antibiotics. All compoundsof this group inhibit humanphospholipase A2 at a concentration of 10~6 molar.Phospholipase A2 [EC 3.1.1.4] plays a major role in the release ofarachidonic acid from phospholipids in the cell membranes1*. Further oxidative metabolism of free arachidonic acid leads to prostaglandins and leukotrienes2).Several of these eicosanoids are potent mediators of diseases, such as inflammation and allergy3). Inhibition of the enzymic activity of phospholipase A2 may therefore be therapeutically beneficial.In our search for naturally occurring inhibitors of phospholipase A2 among secondary metabolites of microorganisms two newinhibitors from the actinomycetes strains R2075 and R2107 were identified which appeared to be closely related to the known peptide antibiotic duramycin. Using a different screening assay for compounds stimulating DNArepair, we found a strain producing duramycin as well as one producing cinnamycin (W. Marki and E. Rommele; unpublished results). In the present communication the taxonomy of these strains and the production, isolation, physico-chemical data and phospholipase inhibition of the newcompoundsduramycins B and C, as well as of duramycin and cinnamycin are described. Experimental results relating to the structural characterization are presented as well. Materials and Methods Microorganism

No abstract

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.