Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.

Abstract

A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum.The antibioticproducing microorganism was characterized and identified as Streptomyces hygroscopicus.The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin.Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 pg/ml.Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi.No activity was observed against gram-positive and gram-negative bacteria.Acute toxicity in mice is low.Cultures of a streptomycete isolated from an Easter Island (Rapa Nui) soil sample were found to inhibit the yeast, Candida albicans, and the dermatophytes, Microsporum gypseum and Trichophyton granulosum; antibacterial activity was only marginal and limited to some grampositive species, such as Sarcina lutea and Staphylococcus aureus; all gram-negative bacteria tested were resistant.The active principle was isolated from the mycelium of the streptomycete