UPTAKE OF 3H-GRISEOFULVIN BY MICRO-ORGANISMS AND ITS CORRELATION WITH SENSITIVITY TO GRISEOFULVIN.

Abstract

A correlation was observed between the sensitivity of different microorganisms to griseofulvin and their ability to take up the antibiotic, especially into their nucleic acid and protein fractions. The insensitive yeasts Candida albicans and Saccharomyces cerevisiae and the bacterium Escherichia coli did not bind an appreciable amount of [4-methoxy-3H] griseofulvin. The poorly sensitive filamentous fungi Aspergillus niger and Neurospora crassa accumulated a considerable quantity of antibiotic, mostly in the water-soluble pool. This was in contrast to the highly sensitive dermatophytes Microsporum gypseum, Trichophyton mentagrophytes and T. persicolor in which the nucleic acid and protein fraction contained about half of the total bound griseofulvin (as relatively stable complexes). It is proposed that uptake of griseofulvin is essential for antibiotic action and that the degree of sensitivity shown by an organism is dependent upon the tendency of its macromolecules to complex with the accumulated griseofulvin. Griseofulvin was not degraded by the insensitive or the poorly sensitive organisms tested. Metabolic products of griseofulvin were detected, however, in culture fluids of the sensitive dermatophytes.