Bacterial cytological profiling identifies transmembrane anion transport as the mechanism of action for a urea-based antibiotic

IF 2.1 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Supramolecular Chemistry Pub Date : 2022-01-02 DOI:10.1080/10610278.2023.2178921

Sarah R. Herschede, R. Salam, Hassan Gneid, Nathalie Busschaert

引用次数: 2

Abstract

ABSTRACT There is a growing fear that bacteria are emerging that are resistant to most known antibiotics, which could lead to an increasing number of fatalities due to bacterial infections. There is therefore an urgent need for the development of novel antibacterial products, preferably with novel mode of actions for which there are no known resistance pathways. We have previously found serendipitously that a simple urea-based compound functions as a potent antibacterial agent. In this manuscript, we use bacterial cytological profiling (BCP) to determine its mechanism of action. BCP reveals that the urea is acting through a membrane-based pathway that is comparable to, but distinct from, the mechanism of cationophore calcimycin. Additional liposome-based assays suggest that the likely mechanism of action of this mono-urea is transmembrane anion transport. This finding highlights that synthetic anionophores could be used as potential antibiotics. Graphical abstract

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细菌细胞学分析确定跨膜阴离子运输作为尿素基抗生素的作用机制

人们越来越担心出现对大多数已知抗生素具有耐药性的细菌，这可能导致因细菌感染而死亡的人数增加。因此，迫切需要开发新的抗菌产品，最好是具有新的作用模式，没有已知的耐药途径。我们以前偶然发现了一种简单的尿素基化合物作为一种有效的抗菌剂。在这篇文章中，我们使用细菌细胞学分析(BCP)来确定其作用机制。BCP表明，尿素通过一种基于膜的途径起作用，这种途径与钙霉素的机制相似，但又不同。其他基于脂质体的分析表明，这种单尿素的作用机制可能是跨膜阴离子运输。这一发现突出表明，人工合成的阴离子载体可以用作潜在的抗生素。图形抽象

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来源期刊

Supramolecular Chemistry 化学-化学综合

CiteScore

3.60

自引率

3.00%

发文量

审稿时长

2.7 months

期刊介绍： Supramolecular Chemistry welcomes manuscripts from the fields and sub-disciplines related to supramolecular chemistry and non-covalent interactions. From host-guest chemistry, self-assembly and systems chemistry, through materials chemistry and biochemical systems, we interpret supramolecular chemistry in the broadest possible sense. Interdisciplinary manuscripts are particularly encouraged. Manuscript types include: high priority communications; full papers; reviews, and; Methods papers, techniques tutorials highlighting procedures and technologies that are important to the field. We aim to publish papers in a timely fashion and as soon as a paper has been accepted and typeset it will be published in electronic form on the Latest articles section of the website. The two most important review criteria are that the paper presents high-quality work that fits generally into the broad spectrum of activities in the supramolecular chemistry field. Under normal circumstances, Supramolecular Chemistry does not consider manuscripts that would be more suitable in a highly specialized journal. This includes, but is not limited to, those based mostly or exclusively on topics such as solid state/X-ray structures, computational chemistry, or electrochemistry. . The two most important review criteria are that the paper presents high-quality work that fits generally into the broad spectrum of activities in the supramolecular chemistry field.