Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Engineering Research Center of Industrial Microbiology of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.
Front Cell Infect Microbiol. 2020 Feb 28;10:84. doi: 10.3389/fcimb.2020.00084. eCollection 2020.
Antibiotic resistance/tolerance has become a severe threat to human and animal health. To combat antibiotic-resistant/tolerant bacteria, it is of significance to improve the efficacy of traditional antibiotics. Here we show that indole potentiates tobramycin to kill stationary-phase cells after a short, combined treatment, with its derivative 5-methylindole being the most potent compound tested and with the absence of ions as a prerequisite. Consistently, this combined treatment also kills various types of persister cells as induced by the protonophore CCCP, nutrient shift, or starvation, as well as methicillin-resistant (MRSA) cells. Importantly, 5-methylindole potentiates tobramycin killing of persisters in a mouse acute skin wound model. Furthermore, 5-methylindole facilitates killing of many strains of gram-positive pathogens such as , and by aminoglycoside antibiotics, whereas it suppresses the action of aminoglycoside against the gram-negative pathogens and . In conclusion, our work may pave the way for the development of indole derivatives as adjuvants to potentiate aminoglycosides against gram-positive pathogens.
抗生素耐药性/耐受性已成为人类和动物健康的严重威胁。为了对抗抗药性/耐受性细菌，提高传统抗生素的疗效具有重要意义。在这里，我们发现吲哚在短时间的联合治疗后增强了妥布霉素对静止期细胞的杀伤作用，其中其衍生物 5-甲基吲哚是测试过的最有效的化合物，并且不需要离子作为前提条件。一致地，这种联合治疗也能杀死由质子载体 CCCP、营养物质转移或饥饿诱导的各种类型的 持留细胞，以及耐甲氧西林金黄色葡萄球菌 (MRSA) 细胞。重要的是，5-甲基吲哚在小鼠急性皮肤创伤模型中增强了妥布霉素对 持留细胞的杀伤作用。此外，5-甲基吲哚促进了氨基糖苷类抗生素对革兰氏阳性病原体 的杀伤，如 和 ，而抑制了氨基糖苷类抗生素对革兰氏阴性病原体 和 的作用。总之，我们的工作可能为开发吲哚衍生物作为增强氨基糖苷类抗生素对革兰氏阳性病原体的增效剂铺平道路。
