通过利用数千个条形码大肠杆菌基因敲除基因筛选，研究人员测试了200种药物的抗菌活性。研究人员分析了药物特异性毒性背后的200万种基因-药物相互作用。基于网络的药物-药物相似性分析表明，抗生素聚集在与其既定类别的作用模式一致的模块中，而非抗生素仍然没有联系。
半数非抗生素聚集成独立的模块，可能揭示了新型抗菌药物的共享和未开发靶点。对外排系统的分析表明，它们对抗生素和非抗生素都有广泛的影响，这表明应在体内仔细研究非抗生素对抗生素交叉耐药性的影响。
据悉，许多非抗生素药物都具有很强的抗菌活性，并会对人体微生物群产生不利影响。这种毒性的机理基础在很大程度上仍然未知。
附：英文原文
Title: Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics
Author: Mariana Noto Guillen, Carmen Li, Brittany Rosener, Amir Mitchell
Issue&Volume: 2024-03-14
Abstract: Numerous nonantibiotic drugs have potent antibacterial activity and can adversely impact the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules consistent with the mode of action of their established classes, while nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for novel antimicrobials. Analysis of efflux systems revealed they widely impact antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.
DOI: adk7368
Source: https://www.science.org/doi/10.1126/science.adk7368