Cotton Kaitlyn, Lieberman Jacob A, Gerasimchuk Nikolay, Wozniak Karen L
Department of Microbiology & Molecular Genetics, Oklahoma State University, Stillwater, OK, USA.
Chemistry Department, Missouri State University, Springfield, MO, USA.
J Med Microbiol. 2025 Sep;74(9). doi: 10.1099/jmm.0.002058.
is an opportunistic fungal pathogen that causes pulmonary cryptococcosis, or an acute or chronic infection in the lungs, and cryptococcal meningitis, an infection of the brain and spinal column, in immunocompromised individuals. Fungal infections are responsible for ~1.7 million deaths each year. In contrast to antibacterial drugs, the quantity of antifungal drugs capable of combating fungal infections remains low. With high toxicity and increased resistance to antifungals in recent years, the importance of finding new options for antifungal therapy is even more crucial. We hypothesized that a series of organoantimony compounds that previously exhibited antifungal activity could serve as effective antifungal drugs. We aimed to evaluate the antifungal activity of these compounds and their mechanism of action. We first evaluated antifungal activity via MIC and minimum fungicidal concentration assay. Next, we evaluated cytotoxicity, followed by mechanistic studies via electron microscopy and RNA sequencing studies. Finally, we evaluated activity using a model. Results showed that several compounds were antifungal and also non-toxic. RNA sequencing identified several differentially regulated genes and pathways, including those associated with membrane transport and formation, ribosome biogenesis and gene expression. Scanning electron microscopy and transmission electron microscopy studies show altered morphology and cellular death following the treatment of with the compounds. Compounds had moderate efficacy in the infection model. These studies show that organoantimony compounds are promising antifungal therapies, and more studies are currently underway to improve efficacy and narrow down their mechanism(s) of antifungal activity.
是一种机会性真菌病原体，可导致肺隐球菌病，即肺部的急性或慢性感染，以及免疫功能低下个体的隐球菌性脑膜炎，即大脑和脊柱的感染。真菌感染每年导致约170万人死亡。与抗菌药物相比，能够对抗真菌感染的抗真菌药物数量仍然很少。由于近年来毒性高且对抗真菌药物的耐药性增加，寻找新的抗真菌治疗选择的重要性更加关键。我们假设一系列先前表现出抗真菌活性的有机锑化合物可以作为有效的抗真菌药物。我们旨在评估这些化合物的抗真菌活性及其作用机制。我们首先通过MIC和最低杀菌浓度测定评估抗真菌活性。接下来，我们评估细胞毒性，然后通过电子显微镜和RNA测序研究进行作用机制研究。最后，我们使用一个模型评估活性。结果表明，几种化合物具有抗真菌作用且无毒。RNA测序鉴定了几个差异调节的基因和途径，包括与膜转运和形成、核糖体生物发生和基因表达相关的基因和途径。扫描电子显微镜和透射电子显微镜研究表明，用这些化合物处理后，形态发生改变且细胞死亡。化合物在感染模型中具有中等疗效。这些研究表明，有机锑化合物是有前景的抗真菌疗法，目前正在进行更多研究以提高疗效并缩小其抗真菌活性机制。
