Essid Rym, Hammami Majdi, Gharbi Dorra, Karkouch Ines, Hamouda Thouraya Ben, Elkahoui Salem, Limam Ferid, Tabbene Olfa
Laboratory of Bioactive Substances, Center of Biotechnology, Ecopark of Borj Cedria, Hammam-Lif, Tunisia.
Laboratory of Aromatic and Medicinal plants, Center of Biotechnology, Ecopark of Borj Cedria, Hammam-Lif, Tunisia.
Appl Microbiol Biotechnol. 2017 Sep;101(18):6993-7006. doi: 10.1007/s00253-017-8442-y. Epub 2017 Aug 1.
The present study aimed to investigate the anti-Candida activity of ten essential oils (EOs) and to evaluate their potential synergism with conventional drugs. The effect on secreted aspartic protease (SAP) activity and the mechanism of action were also explored. The antifungal properties of essential oils were investigated using standard micro-broth dilution assay. Only Cinnamomum verum, Thymus capitatus, Syzygium aromaticum, and Pelargonium graveolens exhibited a broad spectrum of activity against a variety of pathogenic Candida strains. Chemical composition of active essential oils was performed by gas chromatography-mass spectrometry (GC-MS). Synergistic effect was observed with the combinations C. verum/fluconazole and P. graveolens/fluconazole, with FIC value 0.37. Investigation of the mechanism of action revealed that C. verum EO reduced the quantity of ergosterol to 83%. A total inhibition was observed for the combination C. verum/fluconazole. However, P. graveolens EO may disturb the permeability barrier of the fungal cell wall. An increase of MIC values of P. graveolens EO and the combination with fluconazole was observed with osmoprotectants (sorbitol and PEG6000). Furthermore, the combination with fluconazole may affect ergosterol biosynthesis and disturb fatty acid homeostasis in C. albicans cells as the quantity of ergosterol and oleic acid was reduced to 52.33 and 72%, respectively. The combination of P. graveolens and C. verum EOs with fluconazole inhibited 78.31 and 64.72% SAP activity, respectively. To our knowledge, this is the first report underlying the mechanism of action and the inhibitory effect of SAP activity of essential oils in synergy with fluconazole. Naturally occurring phytochemicals C. verum and P. graveolens could be effective candidate to enhance the efficacy of fluconazole-based therapy of C. albicans infections.
本研究旨在调查十种精油（EOs）的抗念珠菌活性，并评估它们与传统药物的潜在协同作用。还探讨了对分泌天冬氨酸蛋白酶（SAP）活性的影响及其作用机制。使用标准微量肉汤稀释法研究了精油的抗真菌特性。只有肉桂、头状百里香、丁香和香叶天竺葵对多种致病性念珠菌菌株表现出广谱活性。通过气相色谱-质谱联用（GC-MS）分析了活性精油的化学成分。观察到肉桂/氟康唑和香叶天竺葵/氟康唑组合具有协同作用，FIC值为0.37。作用机制研究表明，肉桂精油将麦角固醇的量降低到83%。观察到肉桂/氟康唑组合具有完全抑制作用。然而，香叶天竺葵精油可能会扰乱真菌细胞壁的渗透屏障。使用渗透压保护剂（山梨醇和聚乙二醇6000）时，观察到香叶天竺葵精油及其与氟康唑组合的MIC值增加。此外，与氟康唑组合可能会影响白色念珠菌细胞中麦角固醇的生物合成并扰乱脂肪酸稳态，因为麦角固醇和油酸的量分别降低到52.33%和72%。香叶天竺葵和肉桂精油与氟康唑的组合分别抑制了78.31%和64.72%的SAP活性。据我们所知，这是第一份关于精油与氟康唑协同作用的作用机制及其对SAP活性抑制作用的报告。天然存在的植物化学物质肉桂和香叶天竺葵可能是增强基于氟康唑治疗白色念珠菌感染疗效的有效候选物。
