College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China.
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China.
J Ethnopharmacol. 2020 Oct 5;260:113002. doi: 10.1016/j.jep.2020.113002. Epub 2020 Jun 2.
Fungal infections remain a serious problem worldwide that require effective therapeutic strategies. Essential oil of basil (Ocimum basilicum L., BEO) being traditionally used extensively for the treatment of bacterial and fungal infection has a long history. However, the potential mechanism of action was still obscure, especially from the metabolic perspective.
The fungistatic effect of BEO on Candida albicans (C. albicans) was evaluated by measurement of minimum inhibitory concentration (MIC) and morphological analysis. A high-coverage microbial metabolomics approach was utilized to identify the alterations of intracellular metabolites of C. albicans at mid-logarithmic growth phase in response to the subinhibitory concentration of BEO, by using gas chromatography coupled to time-of-fight mass spectrometry (GC-TOFMS). Following the metabolic fingerprinting, systematic network analysis was performed to illustrate the potential mechanism of BEO involved in the suppression of C. albicans.
The damage in cellular membranes of C. albicans treated by BEO above MIC was observed on the scanning electron microscope (SEM) micrographs. Metabolomics results showed that, among 140 intracellular metabolites identified by comparison with reference standards, thirty-four had significantly changed abundances under 0.2 MIC of BEO treatment, mainly involving in central carbon metabolism (glycolysis/gluconeogenesis, pentose phosphate pathway and TCA cycle), amino acids, polyamines and lipids metabolism. Pathway and network analyses further found that fifteen ingredients of BEO mainly terpenoids and phenyl-propanoids, potentially participated in the metabolic regulation and may be responsible for the suppression of C. albicans.
The findings highlighted that integrated microbial metabolomics and network analyses could provide a methodological support in understanding the functional mechanisms of natural antimicrobial agents and contribute to drug discovery.
真菌感染仍然是一个全球性的严重问题,需要有效的治疗策略。罗勒精油(Ocimum basilicum L.,BEO)作为一种传统上广泛用于治疗细菌和真菌感染的药物,具有悠久的历史。然而,其潜在的作用机制仍然不清楚,尤其是从代谢的角度来看。
通过测定最小抑菌浓度(MIC)和形态分析评估 BEO 对白色念珠菌(Candida albicans,C. albicans)的抑菌作用。采用高覆盖度的微生物代谢组学方法,利用气相色谱-飞行时间质谱联用(GC-TOFMS),在对数中期生长阶段,检测亚抑菌浓度 BEO 作用下 C. albicans 细胞内代谢物的变化,从而鉴定出 C. albicans 细胞内代谢物的变化。在代谢指纹图谱的基础上,进行系统的网络分析,以阐明 BEO 抑制 C. albicans 生长的潜在作用机制。
在扫描电子显微镜(SEM)照片中观察到 BEO 处理超过 MIC 时 C. albicans 细胞的细胞膜受损。代谢组学结果表明,通过与对照标准品比较,在 0.2 MIC 的 BEO 处理下,有 34 种细胞内代谢物的丰度有显著变化,主要涉及中央碳代谢(糖酵解/糖异生、磷酸戊糖途径和 TCA 循环)、氨基酸、多胺和脂质代谢。通路和网络分析进一步发现,BEO 的 15 种成分主要为萜类化合物和苯丙烷类化合物,可能参与了代谢调节,可能是抑制 C. albicans 的原因。
这些发现强调了整合微生物代谢组学和网络分析可以为理解天然抗菌药物的功能机制提供方法学支持,并有助于药物发现。