Shi Dongmei, Zhao Yaxin, Yan Hongxia, Fu Hongjun, Shen Yongnian, Lu Guixia, Mei Huan, Qiu Ying, Li Dongmei, Liu Weida
Int J Clin Pharmacol Ther. 2016 May;54(5):343-53. doi: 10.5414/CP202460.
Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.
十一烯酸可有效控制皮肤真菌感染，但其真菌抑制机制尚不清楚。白色念珠菌的菌丝生长和生物膜形成已被公认为是引发皮肤感染和后期播散性感染发展的重要毒力因子。在本研究中，我们试图通过评估白色念珠菌生物膜形成过程中的毒力因子来研究十一烯酸的抗真菌机制。我们发现，十一烯酸能有效抑制白色念珠菌生物膜的形成，最佳浓度高于3 mM。在该化合物存在的情况下，当十一烯酸浓度高于4 mM时，酵母到丝状相的形态转变最终被消除。同时，细胞表面起皱，即使在低浓度药物处理下，扫描电子显微镜下细胞也呈现萎缩外观。另一方面，药物处理降低了分泌天冬氨酸蛋白酶、脂肪酶和磷脂酶等水解酶的转录水平。在药物处理的生物膜条件下，与菌丝形成相关的基因，如HWP1，转录水平也显著降低。这些基因的下调导致在十一烯酸处理的环境中生物膜组织不良。
