Entry of ketoconazole into Candida albicans.
AUTOR(ES)
Boiron, P
RESUMO
To define characteristics that determine the entry of ketoconazole (KTZ) into Candida albicans cells, we studied the uptake of [3H]KTZ. The cells rapidly and markedly concentrated the drug: 30% of the final 80-fold intracellular concentration was attained in less than 1 min, and greater than 60% was attained in 10 min. Penetration of [3H]KTZ at an extracellular concentration higher than 0.1875 microM (0.1 microgram/ml) occurred by a simple diffusion mechanism. At lower concentrations, accumulation of the drug was an active, energy-requiring process, dependent at least in part on glycolysis, and pH dependent (optimal pH, 6.6). The active transport system had a high binding affinity (Km = 50 nM) and a high maximum velocity of uptake (Vmax = 1.4 mumol min-1 10(-7) cells). It was not possible to displace intracellular [3H]KTZ with high concentrations of unlabeled KTZ or other antifungal agents. These findings suggest that KTZ is rapidly taken up, highly concentrated, and tightly bound to cellular components of C. albicans.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=174699Documentos Relacionados
- Primary site of action of ketoconazole on Candida albicans.
- Effect of ketoconazole on isolated mitochondria from Candida albicans.
- Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazole-susceptible and -resistant Candida albicans.
- Growth phase in relation to ketoconazole and miconazole susceptibilities of Candida albicans.
- Effect of ketoconazole on the fungicidal action of amphotericin B in Candida albicans.
