Antifungal activity of spider venom-derived peptide lycosin-I against Candida tropicalis
Antifungal activity of spider venom-derived peptide lycosin-I against Candida tropicalis
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蜘蛛毒肽溶菌素-I 对热带念珠菌的抗真菌活性
DOI：
10.1016/j.micres.2018.08.012
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发表时间：
2018
影响因子：
6.7
通讯作者：
Min Hu
中科院分区：
文献类型：
--
作者：
Li Tan;Le Bai;Ling Wang;Lagu He;Guangdi Li;Wenhan Du;Ting Shen;Zheyi Xiang;Jiali Wu;Zhonghua Liu;Min Hu
念珠菌是人类黏膜和深部组织真菌感染的主要原因，但几乎没有抗真菌治疗可用。在这里，我们展示了溶菌素-I，一种从蜘蛛毒液中分离出来的多肽，对假丝酵母菌具有有效的抗真菌抑制作用。溶菌素-I对氟康唑敏感株和耐氟康唑株的MIC50值分别达到8μg/m L。时间-杀灭动力学分析显示，在作用2小时后，溶菌素-I使氟康唑敏感和耐药热带毛滴虫分离株的集落形成单位/毫升减少约70%。此外，耐盐性分析表明，即使在镁离子存在的情况下，溶菌素-I在较高浓度时仍保持其强大的抗真菌能力。当溶菌素-I的浓度从1×MIC增加到8×MIC时，无论是氟康唑敏感株还是氟康唑耐药株，生物膜代谢活性均显著降低。生物被膜抑制浓度(BIC_(50))和生物膜清除浓度(BEC_(50))分别约为32μg/m L和128μg/m L。激光共聚焦扫描显微镜显示，Cy5标记的Lycoin-I主要定位在细胞质中，Lycoin-I可能在穿过细胞壁和细胞膜后定位于细胞质中。总体而言，我们的工作表明，溶菌素-I是一种有效的抗真菌药物，具有高效、高耐盐性和强大的抗生物被膜特性。
Candida species are a major cause of human mucosal and deep tissue fungal infections, but few antifungal treatments are available. Here, we showed that lycosin-I, a peptide isolated from venom of the spider Lycosa singoriensis, acted as a potent antifungal inhibitor against Candida species. The MIC50 values of lycosin-I reached 8 μg/mL to treat fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Time-kill kinetics assays revealed that after a 2-hour exposure, lycosin-I reduced colony-forming units/mL in fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates approximately 70%. Furthermore, salinity tolerance assays suggested that even in the presence of Mg2+, lycosin-I maintained its potent antifungal ability at a high concentration. When the concentration of lycosin-I was increased from 1 × MIC to 8 × MIC, a significant decrease of the biofilm metabolic activity was observed in both fluconazole-susceptible and fluconazole-resistant C. tropicalis isolates. Moreover, the biofilm inhibitory concentration 50 (BIC50) and the biofilm eradicating concentration 50 (BEC50) were approximately 32 μg/mL and 128 μg/mL, respectively. Confocal laser scanning microscopy showed the localization of CY5-labeled lycosin-I mainly in the cell cytoplasm, and lycosin-I was likely to be localized in the cytoplasm after its transportation across the cell wall and membrane. Overall, our work shows that lycosin-I is a potent antifungal agent with a high efficacy, a high salinity tolerance, and potent anti-biofilm properties.