Mode of Action of Miconazole on Candida albicans: Effect on Growth, Viability and K+ Release

Miconazole at 10 p g ml-l inhibited the growth of exponential phase cultures of Candida albicans and released intracellular K+. Higher concentrations of rniconazole were, however, required to cause cell death: at neutral pH, complete killing occurred at 30 pg ml-l, while at pH 3.0 or 4.5, there was only partial killing with miconazole up to 80 p g rnl-l. Efficient killing of C. albicans by miconazole occurred both at low temperature and when cells were incubated in buffer alone. It is proposed that both the fungistatic and fungicidal actions of miconazole are due to its direct interaction with the cellular membranes of C. albicans rather than to an inhibition of biochemical reactions. Divalent cations protected C. albicans from both the fungistatic and fungicidal effects of miconazole and this was probably due to a competition between the ions and miconazole in its positively charged form for nega-tively charged binding sites. Candida albicans increased in resistance to miconazole-induced Kf release during the stationary phase of a batch culture. Development of this resistance required efficient aeration