Systematic screen uncovers regulator contributions to chemical cues in Escherichia coli.

IF 7.2 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2025-07-22 eCollection Date: 2025-07-01 DOI:10.1371/journal.pbio.3003260
Christoph Binsfeld, Roberto Olayo-Alarcon, Lucía Pérez Jiménez, Morgane Wartel, Mara Stadler, André Mateus, Christian Müller, Ana Rita Brochado
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引用次数: 0

Abstract

In Gram-negative bacteria, the uptake and export of a wide range of molecules, including antibiotics, is facilitated by porins and efflux pumps. Because of their role in regulating small molecule permeability of the outer and inner membrane, these transport machineries are tightly regulated at the transcriptional and post-transcriptional levels. However, regulation of transport by external chemical cues remains poorly understood. Here we investigated transcriptional regulation of three prominent transporter genes in Escherichia coli across 94 defined chemical cues, and simultaneously mapped the contributions of the key regulators MarA, SoxS and Rob to promoter activity. One third of all tested compounds triggered transcriptional changes, the majority of which were previously unknown. Importantly, we exposed main drivers of transport control in E. coli, e.g., bacteriostatic but not bactericidal antibiotics trigger the expression of efflux pumps, and Rob contributes to ~1/3 of all measured transcriptional changes, thereby emerging as a more prominent regulator of transport than previously thought. We showcase the potential of our resource by elucidating the molecular mechanism of antibiotic antagonisms with widely consumed caffeine in E. coli. Altogether, our analysis provides a quantitative overview of how different regulators orchestrate the transcriptional response of major transport determinants to environmental chemical cues.

系统筛选揭示了调节剂对大肠杆菌化学线索的贡献。
在革兰氏阴性菌中,包括抗生素在内的多种分子的摄取和输出是由孔蛋白和外排泵促进的。由于它们在调节外膜和内膜的小分子通透性方面的作用,这些运输机制在转录和转录后水平上受到严格调控。然而,外部化学信号对运输的调节仍然知之甚少。在这里,我们研究了大肠杆菌中三个主要转运体基因在94种确定的化学线索中的转录调控,并同时绘制了关键调控因子MarA、SoxS和Rob对启动子活性的贡献。在所有测试的化合物中,有三分之一触发了转录变化,其中大部分是以前未知的。重要的是,我们揭示了大肠杆菌中运输控制的主要驱动因素,例如,抑菌而非杀菌抗生素触发外排泵的表达,并且Rob贡献了所有测量的转录变化的约1/3,从而成为比以前认为的更突出的运输调节因子。我们通过阐明大肠杆菌中广泛消耗的咖啡因对抗生素拮抗的分子机制,展示了我们资源的潜力。总之,我们的分析提供了一个定量的概述,不同的调节如何协调主要运输决定因素对环境化学线索的转录反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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