Department of Mycology and Genetics, Faculty of Biological Sciences, University of Wrocław, Wrocław, Poland.
Laboratory of Microscopic Techniques, Faculty of Biological Sciences, University of Wrocław, Wrocław, Poland.
Arch Microbiol. 2024 Mar 12;206(4):153. doi: 10.1007/s00203-024-03894-9.
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.
3-溴丙酮酸（3BP）以其强大的抗癌特性而闻名，对致病性真菌新生隐球菌也具有显著的疗效。到目前为止，已经证明 3BP 的主要杀菌活性是基于 ATP 耗竭和细胞内谷胱甘肽水平的降低。本研究采用了广泛的方法来进一步研究 3BP 对新生隐球菌细胞的作用机制。使用流式细胞术可以彻底检查它们在 3BP 处理过程中的存活情况，而使用电子显微镜观察则可以注意到细胞形态的变化。利用钌红，研究表明线粒体途径可能会引发程序性细胞死亡以响应 3BP。自由基生成和基因表达变化的分析支持这一假设。这些发现增强了对 3BP 在真菌细胞中的作用机制的理解，为将其作为抗隐球菌病的治疗剂的潜在应用铺平了道路。
