Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.
J Microbiol. 2019 May;57(5):405-412. doi: 10.1007/s12275-019-8511-2. Epub 2019 Feb 22.
Xanthorrhizol (XTZ), isolated from Curcuma xanthorrhiza, has potent antifungal and antibacterial activity. It shows very strong activity against Gram-positive bacteria, such as Streptococcus mutans and Staphylococcus aureus, but is generally not active against Gram-negative bacteria. In this study, we explored the possibility of using a combination strategy for expanding the antimicrobial spectrum of XTZ against Gram-negative bacteria. To take advantage of XTZ being a food-grade material, 10 food-grade or generally recognized as safe (GRAS) antimicrobial compounds with low toxicities were selected for combination therapy. In addition, polymyxin B nonapeptide (PMBN), which is less toxic than polymyxin B, was also selected as an outer membrane permeabilizer. The antibacterial activity of various double or triple combinations with or without XTZ were assayed in vitro against four Gram-negative bacterial species (Escherichia coli, Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Vibrio cholerae), with synergistic combinations exhibiting clear activity subjected to further screening. The combinations with the greatest synergism were XTZ + PMBN + nisin, XTZ + PMBN + carvacrol, and XTZ + PMBN + thymol. These combinations also showed potent antimicrobial activity against Shigella spp., Yersinia enterocolitica, and Acinetobacter baumannii. In time-kill assays, the three combinations achieved complete killing of E. coli within 2 h, and S. Typhi and V. cholera within 15 min. This is the first report on expanding the activity spectrum of XTZ against Gram-negative bacteria through combination with PMBN and food-grade or GRAS substances, with the resulting findings being particularly useful for increasing the industrial and medical applications of XTZ.
姜黄素（XTZ）从姜黄中分离出来，具有很强的抗真菌和抗菌活性。它对革兰氏阳性菌（如变形链球菌和金黄色葡萄球菌）显示出很强的活性，但通常对革兰氏阴性菌没有活性。在这项研究中，我们探索了使用组合策略扩大 XTZ 对革兰氏阴性菌抗菌谱的可能性。为了利用 XTZ 是一种食品级材料，选择了 10 种食品级或一般公认安全（GRAS）的低毒性抗菌化合物进行联合治疗。此外，还选择了毒性比多粘菌素 B 低的多粘菌素 B 九肽（PMBN）作为外膜通透剂。用各种双或三组合物与或不与 XTZ 进行体外抗菌活性测定，针对四种革兰氏阴性细菌（大肠杆菌、伤寒沙门氏菌血清型 Typhi、鼠伤寒沙门氏菌血清型 Typhimurium 和霍乱弧菌），具有协同作用的组合物进一步进行了筛选。协同作用最大的组合是 XTZ + PMBN + 乳链菌肽、XTZ + PMBN + 香芹酚和 XTZ + PMBN + 百里酚。这些组合对志贺氏菌、肠耶尔森菌和鲍曼不动杆菌也表现出很强的抗菌活性。在时间杀伤试验中，三种组合在 2 小时内完全杀死大肠杆菌，在 15 分钟内杀死伤寒沙门氏菌和霍乱弧菌。这是首次报道通过与 PMBN 和食品级或 GRAS 物质联合扩大 XTZ 对革兰氏阴性菌活性谱的研究，研究结果对于增加 XTZ 的工业和医学应用特别有用。
