3-Bromopyruvate: A novel antifungal agent against the human pathogen Cryptococcus neoformans

Dylag, Mariusz;Lis, Paweł;Niedźwiecka, Katarzyna;Ko, Young H.;Ułaszewski, Stanisław;et.al.
(2013) Biochemical and Biophysical Research Communications — Vol. 434, n° 2, p. 322-327 (2013)

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Authors
  • Dylag, MariuszInstitute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland
    Author
  • Lis, PawełInstitute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland
    Author
  • Niedźwiecka, KatarzynaInstitute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland
    Author
  • Ko, Young H.KoDiscovery, LLC, UM BioPark, Baltimore, USA
    Author
  • Goffeau, AndréUCLouvain
    Author
  • Ułaszewski, StanisławInstitute of Genetics and Microbiology, University of Wroclaw, Wroclaw, Poland
    Author
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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. © 2013 Elsevier Inc.
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Dylag, M., Lis, P., Niedźwiecka, K., Ko, Y. H., Pedersen, P. L., Goffeau, A., & Ułaszewski, S. (2013). 3-Bromopyruvate: A novel antifungal agent against the human pathogen Cryptococcus neoformans. Biochemical and Biophysical Research Communications, 434(2), 322-327. https://doi.org/10.1016/j.bbrc.2013.02.125 (Original work published 2013)