Enhancement of the antibiofilm activity of amphotericin B by polyamine biosynthesis inhibitors
Enhancement of the antibiofilm activity of amphotericin B by polyamine biosynthesis inhibitors
复制标题
多胺生物合成抑制剂增强两性霉素 B 的抗生物膜活性
DOI：
10.1016/j.ijantimicag.2015.02.021
复制
发表时间：
2015-07-01
影响因子：
10.8
通讯作者：
Cao, YingYing
中科院分区：
文献类型：
--
作者：
Liao, ZeBin;ZhangGuan, XuanZi;Cao, YingYing
本研究旨在探讨多胺生物合成抑制剂对白念珠菌生物被膜抑制活性的影响及其机制。当与多胺生物合成抑制剂1，4-二氨基-2-丁酮（DAB）和α-二氟甲基鸟氨酸（DFMO）组合使用时，AmB的生物膜活性显著增强。进一步的研究表明，DAB和DFMO也增强了其他几种抗真菌药物的抗菌膜活性。此外，AmB和多胺生物合成抑制剂的组合导致细胞内活性氧水平的增加。此外，caspase的活性和caspase编码基因CaMCA 1的转录大大增加后，与多胺生物合成抑制剂和AmB的组合处理。一致的是，生物膜形成的Delta camca 1突变体表现出更大的活力和较低的caspase活性比野生型菌株联合治疗后。这些数据提供了有用的信息，开发新的策略，以提高抗真菌药物的抗真菌膜活性。(C)2015年Elsevier B. V.和国际化疗学会。All rights reserved.
The aim of this study was to investigate the effect of polyamine biosynthesis inhibitors on the activity of amphotericin B (AmB) against Candida albicans biofilms and to clarify the underlying mechanisms. The antibiofilm activity of AmB was significantly enhanced when used in combination with the polyamine biosynthesis inhibitors 1,4-diamino-2-butanone (DAB) and alpha-difluoromethylornithine (DFMO). Further study showed that DAB and DFMO also enhanced the antibiofilm activity of several other antifungal agents. Moreover, the combination of AmB and polyamine biosynthesis inhibitors resulted in an increase in intracellular levels of reactive oxygen species. In addition, caspase activity and transcription of the caspase-encoding gene CaMCA1 were greatly increased upon combined treatment with polyamine biosynthesis inhibitors and AmB. Consistently, the biofilm formed by a Delta camca1 mutant exhibited greater viability and lower caspase activity than that of the wild-type strain upon combined treatment. These data provide useful information for the development of new strategies to enhance the antibiofilm activities of antifungal agents. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.