School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
Xinjiang Production and Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin/College of Life Science, Tarim University, Alar, 843300, Xinjiang, People's Republic of China.
Appl Microbiol Biotechnol. 2020 Jun;104(11):5039-5052. doi: 10.1007/s00253-020-10559-2. Epub 2020 Apr 4.
Candida albicans invasion is one of the most serious fungal infections in clinical history. In recent years, because of the widespread use of immunosuppressive drugs, chemotherapy drugs, glucocorticoids, and broad-spectrum antibiotics, serious drug resistance has been reported; therefore, a new type of antifungal drug needs to be developed. In this study, we found that Nerol (NEL) had strong antimicrobial activity and 0.77 μL/mL NEL was the minimum inhibitory concentration (MIC) effective against C. albicans. We determined the change of the growth curve of NEL for C. albicans, to identify the trend of NEL activity against C. albicans. Through the determination of the ergosterol content and glucose-induced extracellular fluid acidification of NEL on C. albicans, we found that NEL inhibits the growth of C. albicans by destroying cell membranes. This finding was also supported by the expression of SAP (secreted aspartyl proteinase) involved in cell membrane synthesis. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and PAS (periodic acid-Schiff) staining were conducted to prove that NEL had the ability to treated mouse oral C. albicans infection and vaginal C. albicans infection. This research may help us to investigate new antimicrobial agents for treating C. albicans infections. KEY POINTS: • NEL can inhibit the growth of C. albicans. • NEL destroys the cell membrane formation and permeability of C. albicans. • NEL can treat vulvovaginal candidiasis and oropharyngeal candidiasis in mice. • NEL could be used as a possible antifungal agent.
白色念珠菌侵袭是临床历史上最严重的真菌感染之一。近年来，由于免疫抑制剂、化疗药物、糖皮质激素和广谱抗生素的广泛应用，已报道严重的耐药性；因此，需要开发新型抗真菌药物。在这项研究中，我们发现 Nerol（NEL）具有很强的抗菌活性，0.77 μL/mL 的 NEL 是对白念珠菌有效的最小抑菌浓度（MIC）。我们确定了 NEL 对白色念珠菌生长曲线的变化，以确定 NEL 对白念珠菌活性的趋势。通过测定 NEL 对白色念珠菌中麦角固醇含量和葡萄糖诱导的细胞外液酸化的影响，我们发现 NEL 通过破坏细胞膜来抑制白色念珠菌的生长。这一发现也得到了参与细胞膜合成的 SAP（分泌天冬氨酸蛋白酶）表达的支持。最后，通过表型研究、集落形成单位（CFU）计数和 PAS（过碘酸希夫）染色的证明，表明 NEL 具有治疗小鼠口腔白色念珠菌感染和阴道白色念珠菌感染的能力。这项研究可能有助于我们研究治疗白色念珠菌感染的新抗菌药物。
NEL 可以抑制白色念珠菌的生长。
NEL 破坏白色念珠菌的细胞膜形成和通透性。
NEL 可用于治疗小鼠的外阴阴道念珠菌病和口咽念珠菌病。
NEL 可用作一种潜在的抗真菌药物。
