Effects of pentamidine isethionate on Saccharomyces cerevisiae.
AUTOR(ES)
Ludewig, G
RESUMO
We used Saccharomyces cerevisiae as a model system in which to examine the mechanism of action of the anti-Pneumocystis drug pentamidine. Pentamidine at low concentrations inhibited S. cerevisiae growth on nonfermentable carbon sources (50% inhibitory concentration [IC50] of 1.25 micrograms/ml in glycerol). Pentamidine inhibited growth on fermentable energy sources only at much higher concentrations (IC50 of 250 micrograms/ml in glucose). Inhibition at low pentamidine concentrations in glycerol was due to cytostatic activity rather than cytotoxic or mutagenic activity. Pentamidine also rapidly inhibited respiration by intact yeast cells, although inhibitory concentrations were much higher than those inhibitory to growth (IC50 of 100 micrograms/ml for respiration). Pentamidine also induced petite mutations, although only at concentrations much higher than those required for growth inhibition. These results suggest that a function essential for respiratory growth is inhibited by pentamidine and that pentamidine affects mitochondrial processes. We propose the hypothesis that the primary cellular target of pentamidine in S. cerevisiae is the mitochondrion.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=188161Documentos Relacionados
- Characterization of the PNT1 pentamidine resistance gene of Saccharomyces cerevisiae.
- Genetic effects of methyl benzimidazole-2-yl-carbamate on Saccharomyces cerevisiae.
- Effects of Ty insertions on HIS4 transcription in Saccharomyces cerevisiae.
- Effects of metals on acetyl-coenzyme A carboxylase activity of Saccharomyces cerevisiae.
- Effects of inositol starvation on phospholipid and glycan syntheses in Saccharomyces cerevisiae.
