Abstract
3-Bromopyruvate (3BP), known for its potent anticancer properties, also exhibits remarkable efficacy against the pathogenic fungus Cryptococcus neoformans. So far it has been proven that the main fungicidal activity of 3BP is based on ATP depletion and a reduction of intracellular level of glutathione. The presented study includes a broad range of methods to further investigate the mechanistic effects of 3BP on C. neoformans cells. The use of flow cytometry allowed a thorough examination of their survival during 3BP treatment, while observations using electron microscopy made it possible to note the changes in cellular morphology. Utilizing ruthenium red, the study suggests a mitochondrial pathway may initiate programmed cell death in response to 3BP. Analysis of free radical generation and gene expression changes supports this hypothesis. These findings enhance comprehension of 3BP's mechanisms in fungal cells, paving the way for its potential application as a therapeutic agent against cryptococcosis.
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Acknowledgements
The authors are grateful to Prof. Stanisław Ułaszewski for initiating the broad study on 3BP. Also, the authors would like to thank Marek Chmielewski for his technical help.
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Conceptualization, KP; methodology, KP, RA, MK and JS; formal analysis, KP; investigation, KP, RA, MK and JS; writing—original draft preparation, KP; writing—review and editing, KP, RA, MK, JS and MC; supervision, KP; All authors have read and agreed to the published version of the manuscript.
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Communicated by Yusuf Akhter.
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Przywara, K., Adamski, R., Książczyk, M. et al. 3-bromopyruvate induces morphological alteration and may initiate programmed cell death in Cryptococcus neoformans cells. Arch Microbiol 206, 153 (2024). https://doi.org/10.1007/s00203-024-03894-9
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DOI: https://doi.org/10.1007/s00203-024-03894-9