Abstract

Cryptococcus neoformans is an important opportunistic fungal pathogen that causes various infections. Here, the antifungal and antibiofilm activities of plumbagin against C. neoformans and the underlying mechanisms were evaluated. The minimum inhibitory concentration (MIC) of plumbagin against C. neoformans H99 was 8 μg ml⁻¹. Plumbagin disrupted the cell membrane integrity and reduced the metabolic activities of C. neoformans H99. C. neoformans H99 biofilm cells were damaged by plumbagin at a concentration of 64 μg ml⁻¹, whereas 48-h mature biofilms were dispersed at a plumbagin concentration of 128 μg ml⁻¹. Whole-transcriptome analysis of plumbagin-treated C. neoformans H99 in the biofilm and planktonic states identified differentially expressed genes enriched in several important cellular processes (cell membrane, ribosome biogenesis, fatty acid synthesis, melanin and capsule production). Notably, plumbagin damaged biofilm cells by downregulating FAS1 and FAS2 expression. Thus, plumbagin can be exploited as an antifungal agent to combat C. neoformans-related infections.

摘要

新型隐球菌是一种重要的机会性真菌病原体，可引起多种感染。在这里，评估了白花素对C. neoformans的抗真菌和抗生物膜活性及其潜在机制。铅黄素对C. neoformans H99 的最小抑制浓度 (MIC) 为 8 μg ml ^-1。Plumbagin 破坏了细胞膜的完整性并降低了C. neoformans H99 的代谢活动。C.neoformans H99 生物膜细胞被 64 μg ml ^-1浓度的铅黄素破坏，而 48 小时成熟的生物膜在 128 μg/ml ^{-1的铅黄素浓度下分散}. 在生物膜和浮游状态下，对白杨素处理的新隐球菌H99 进行全转录组分析，确定了富集在几个重要细胞过程（细胞膜、核糖体生物发生、脂肪酸合成、黑色素和胶囊产生）中的差异表达基因。值得注意的是，白铅素通过下调 FAS1 和 FAS2 的表达来破坏生物膜细胞。因此，可以利用白铅素作为抗真菌剂来对抗与新生念珠菌相关的感染。