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Effects of pentamidine isethionate on Saccharomyces cerevisiae
Journal article   Open access   Peer reviewed

Effects of pentamidine isethionate on Saccharomyces cerevisiae

G Ludewig, J M Williams, Y Li and C Staben
Antimicrobial agents and chemotherapy, Vol.38(5), pp.1123-1128
05/1994
DOI: 10.1128/aac.38.5.1123
PMCID: PMC188161
PMID: 8067749
url
https://doi.org/10.1128/aac.38.5.1123View
Published (Version of record) Open Access

Abstract

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.
 Saccharomyces cerevisiae - metabolism Oxygen Consumption - drug effects Saccharomyces cerevisiae - genetics Genotype Indicators and Reagents Saccharomyces cerevisiae - drug effects Mitochondria - metabolism Mitochondria - drug effects Mutagenesis - drug effects Pentamidine - pharmacology

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