Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.
Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay.
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DOI：
10.1021/acsinfecdis.3c00049
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发表时间：
2023-08-11
影响因子：
5.3
通讯作者：
Auer, Manfred
中科院分区：
文献类型：
--
作者：
Pham, Nhan T.;Alves, Joana;Sargison, Fiona A.;Cullum, Reiko;Wildenhain, Jan;Fenical, William;Butler, Mark S.;Mead, David A.;Duggan, Brendan M.;Fitzgerald, J. Ross;La Clair, James J.;Auer, Manfred
抗生素耐药性已成为全球公共卫生威胁，迫切需要开发用于治疗由多重耐药细菌引起的感染的新型疗法。金黄色葡萄球菌是一种主要的人类和动物病原体，导致全球高水平的发病率和死亡率。S.巨噬细胞中的金黄色葡萄球菌有助于免疫逃避、传播和对抗生素治疗的恢复。在这里，我们提出了一个共聚焦荧光成像检测监测巨噬细胞感染的绿色荧光蛋白（GFP）标记的S。金黄色葡萄球菌作为一线工具，以确定抗生素铅。该测定与纳米级化学分析相结合，以促进新的活性利福霉素类似物的发现。我们的研究结果表明，一个有前途的新方法，用于识别抗菌化合物与巨噬细胞内的活动。这里鉴定的抗生素可能是我们应对沉默的抗菌素耐药性大流行的有用补充。
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. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus 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 S. aureus 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.
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