Microbial metabolomics and network analysis reveal fungistatic effect of basil (Ocimum basilicum) oil on Candida albicans

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.