School of Biological Sciences, The University of Edinburgh, The King's Buildings, Edinburgh EH9 3BF, U.K.
The Roslin Institute, The University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, U.K.
ACS Infect Dis. 2023 Aug 11;9(8):1499-1507. doi: 10.1021/acsinfecdis.3c00049. Epub 2023 Jul 11.
Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.
抗菌药物耐药性已成为全球公共卫生威胁，因此迫切需要开发新型疗法来治疗由耐多药细菌引起的感染。 是一种主要的人兽共患病病原体，在全球范围内导致高发病率和死亡率。 在巨噬细胞中的细胞内存活有助于免疫逃避、传播和对抗生素治疗的恢复能力。 在这里，我们提出了一种用于监测绿色荧光蛋白 (GFP) 标记的 感染巨噬细胞的共聚焦荧光成像测定法，作为识别抗生素先导化合物的一线工具。 该测定法与纳米级化学分析相结合，有助于发现一种新型、有效的利福霉素类似物。 我们的研究结果表明，这为鉴定具有巨噬细胞细胞内活性的抗菌化合物提供了一种很有前途的新方法。 这里鉴定的抗生素可能是应对抗菌药物耐药性这一无声流行疾病的有力武器的有益补充。
