期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms23052637
关键词
energy-coupling factor transporters; antimicrobials; B-type vitamins; bacterial uptake assay; screening
We report a novel whole-cell screening assay using Lactobacillus casei as a model microorganism to identify inhibitors of energy-coupling factor (ECF) transporters. This target, which is promising and underexplored, has important pharmacological potential by modulating vitamin homeostasis in bacteria, and is absent in humans. The assay provides an alternative, cost-effective, and fast solution to demonstrate the involvement of these membrane transporters in a native biological environment.
Herein, we report a novel whole-cell screening assay using Lactobacillus casei as a model microorganism to identify inhibitors of energy-coupling factor (ECF) transporters. This promising and underexplored target may have important pharmacological potential through modulation of vitamin homeostasis in bacteria and, importantly, it is absent in humans. The assay represents an alternative, cost-effective and fast solution to demonstrate the direct involvement of these membrane transporters in a native biological environment rather than using a low-throughput in vitro assay employing reconstituted proteins in a membrane bilayer system. Based on this new whole-cell screening approach, we demonstrated the optimization of a weak hit compound (2) into a small molecule (3) with improved in vitro and whole-cell activities. This study opens the possibility to quickly identify novel inhibitors of ECF transporters and optimize them based on structure-activity relationships.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据