Uptake of Griseofulvin by the Sensitive Dermatophyte, Microsporum gypseum

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Abstract
Actively growing cultures of M. gypseum took up large amounts of griseofulvin-(4-methoxy-H3) from the medium. Initially, most of the material could be extracted with hot water, but there was a continuing increase in firmly bound forms of the antibiotic. The fungus accumulated griseofulvin intra-cellularly to a level up to 100 times that present in the medium. The process appeared to involve two phases. A small amount of griseofulvin was bound almost instantaneously. This binding was independent of the culture conditions or cell viability. The second stage was prolonged and was governed by the different factors controlling active metabolism, but it proceeded in organisms whose growth had been inhibited by the antibiotic itself or by limited nutrients. This stage required a supply of metabolic energy, since it was temperature-dependent, needed an exogenous energy source, and was completely inhibited by sodium-azide or 2,4-dinitrophenol. Uptake was optimal at pH 5.5 to 6.5. Synthesis of a transport system is probably required, since uptake is prevented by p-fluorophenylalanine. Heat-killed cells did not take up griseofulvin beyond the small amount bound instantly.