Munro Lachlan Jake, Kell Douglas B
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Lyngby, Denmark.
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK.
Antibiotics (Basel). 2022 Aug 19;11(8):1129. doi: 10.3390/antibiotics11081129.
Antibiotic resistance is a major global healthcare issue. Antibiotic compounds cross the bacterial cell membrane via membrane transporters, and a major mechanism of antibiotic resistance is through modification of the membrane transporters to increase the efflux or reduce the influx of antibiotics. Targeting these transporters is a potential avenue to combat antibiotic resistance. In this study, we used an automated screening pipeline to evaluate the growth of a library of 447 transporter knockout strains exposed to sub-inhibitory concentrations of 18 diverse antimicrobials. We found numerous knockout strains that showed more resistant or sensitive phenotypes to specific antimicrobials, suggestive of transport pathways. We highlight several specific drug-transporter interactions that we identified and provide the full dataset, which will be a useful resource in further research on antimicrobial transport pathways. Overall, we determined that transporters are involved in modulating the efficacy of almost all the antimicrobial compounds tested and can, thus, play a major role in the development of antimicrobial resistance.
抗生素耐药性是一个重大的全球医疗保健问题。抗生素化合物通过膜转运蛋白穿过细菌细胞膜，而抗生素耐药性的一个主要机制是通过修饰膜转运蛋白来增加抗生素的外排或减少其流入。针对这些转运蛋白是对抗抗生素耐药性的一个潜在途径。在本研究中，我们使用了一个自动化筛选流程来评估447种转运蛋白敲除菌株文库在暴露于18种不同抗菌药物的亚抑制浓度下的生长情况。我们发现了许多对特定抗菌药物表现出更强耐药或敏感表型的敲除菌株，这暗示了转运途径。我们重点介绍了我们鉴定出的几种特定的药物 - 转运蛋白相互作用，并提供了完整的数据集，这将成为进一步研究抗菌药物转运途径的有用资源。总体而言，我们确定转运蛋白参与调节几乎所有测试抗菌化合物的疗效，因此在抗生素耐药性的发展中可能起主要作用。
