化学
运输机
金黄色葡萄球菌
蛋白质组
细菌
平衡
跨膜蛋白
生物化学
行动方式
生物物理学
细胞生物学
受体
生物
遗传学
基因
作者
Luke E. Brennan,Lokesh Kumar Kumawat,Magdalena Piatek,Airlie J. Kinross,Daniel A. McNaughton,Luke A. Marchetti,Conor Geraghty,Conor Wynne,Hua Tong,Oisín N. Kavanagh,Finbarr O’Sullivan,Chris S. Hawes,Philip A. Gale,Kevin Kavanagh,Robert B. P. Elmes
出处
期刊:Chem
[Elsevier]
日期:2023-11-01
卷期号:9 (11): 3138-3158
被引量:4
标识
DOI:10.1016/j.chempr.2023.07.014
摘要
Artificial transmembrane ion transporters have proposed applicability to medicinal chemistry, where perturbation of normal cellular homeostasis has already been shown to induce apoptosis in mammalian cells; however, this effect has not been observed in bacteria. In this study, we report the synthesis and structural characterization of a new class of fluorescent anionophores that effectively kill Gram-positive bacteria by disrupting normal Na+ and Cl− concentrations. The so-called “squindoles” take advantage of both NH and CH hydrogen-bonding interactions to bind chloride with high affinity and act as efficient anion transporters, as measured by lipid vesicle transport assays. The most active transporter shows potent inhibitory activity against Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA). Cell-based assays and label-free quantitative proteomic profiling suggest that the mode of action is directly related to the anion-transport ability, whereby an influx of chloride into bacterial cells significantly affects their proteome and induces several known stress responses.
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