[The mode of action of a nonpolyenic antifungal (desertomycin) produced by a strain of Streptomyces spectabilis].
A metabolite with antifungal activity, of non polyenic macrolide structure, was extracted and purified from the culture supernatant of a soil-isolated Streptomyces spectabilis strain, BT 352. This product was found to be related to (or being) desertomycin. Six yeast and five filamentous fungus strains were used to determine minimum concentration of the metabolite that inhibits growth by 80% (IMC); it was established at 50 micrograms/mL for the fungi and at 100 micrograms/mL or more for the yeasts tested. Short-term genotoxicity tests showed no antifungal effect on the bacterial genome, and desertomycin at concentration levels of 100 micrograms/mL or more affected protein synthesis. The antifungal metabolite had no immediate inhibiting effect upon yeast respiration, even at high concentrations; however, the respiration activity of cells grown in the presence of subinhibiting doses and collected during their growth phase was reduced by as much as 40%. Saccharomyces uvarum spheroplast regeneration in a liquid medium containing desertomycin was inhibited at doses fivefold weaker than the IMC determined with intact cells. Contrary to amphotericin B, desertomycin subinhibiting doses do not modify, and if so lightly, the yeast latent phase or the spheroplast wall regeneration phase, thus indicating a fungicidal action. Moreover, following a 30-min contact with desertomycin subinhibiting and inhibiting doses, yeasts liberated potassium in large amounts, indicating that plasma membranes were affected.
Benallaoua
S
S
Laboratoire de biochimie microbienne, Faculté de pharmacie, Nancy, France.
Nguyen Van
P
P
De Meo
M P
MP
Coulon
J
J
Dumenil
G
G
Bonaly
R
R
D000666:Amphotericin B / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D005656:Fungal Proteins / Q000096:biosynthesis / Q000187:drug effects; D005658:Fungi / Q000187:drug effects*; D005798:Genes, Bacterial / Q000187:drug effects; D008055:Lipids / Q000032:analysis; D018942:Macrolides; D009152:Mutagenicity Tests; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D013014:SOS Response, Genetics; D012440:Saccharomyces / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D012988:Soil Microbiology; D013104:Spheroplasts / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D015003:Yeasts / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D005656:Fungal Proteins; D008055:Lipids; D018942:Macrolides; D014415:Tunicamycin; C042503:desertomycin; D000666:Amphotericin B; D003513:Cycloheximide; D011188:Potassium
Recherches sur le mode d'action d'un antifongique non polyénique (désertomycine) produit par une souche de Streptomyces spectabilis.