title: 3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans.
abstract: We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug.
authors.affiliation: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Dyląg
authors.forename: Paweł
authors.initials: P
authors.lastname: Lis
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niedźwiecka
authors.forename: Young H
authors.initials: YH
authors.lastname: Ko
authors.forename: Peter L
authors.initials: PL
authors.lastname: Pedersen
authors.forename: Andre
authors.initials: A
authors.lastname: Goffeau
authors.forename: Stanisław
authors.initials: S
authors.lastname: Ułaszewski
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001692:Biological Transport; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000472:pathogenicity; D015725:Fluconazole / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011773:Pyruvates / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D011773:Pyruvates; C017092:bromopyruvate; D000666:Amphotericin B; D000255:Adenosine Triphosphate; D015725:Fluconazole; D005978:Glutathione