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.

摘要

人们越来越担心，对大多数已知抗生素具有抗药性的细菌正在出现，这可能导致细菌感染导致的死亡人数不断增加。因此，迫切需要开发新型抗菌产品，优选具有尚无已知耐药途径的新型作用模式。我们之前偶然发现一种简单的尿素化合物可以作为有效的抗菌剂。在这篇手稿中，我们使用细菌细胞学分析（BCP）来确定其作用机制。BCP 揭示尿素通过基于膜的途径发挥作用，该途径与阳离子载体钙霉素的机制相似但又不同。其他基于脂质体的测定表明，这种单脲的可能作用机制是跨膜阴离子转运。