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Binsfeld, C.* ; Olayo-Alarcon, R. ; Pérez Jiménez, L.* ; Wartel, M.* ; Stadler, M. ; Mateus, A.* ; Müller, C.L. ; Brochado, A.R.*

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

PLoS Biol. 23, 28:e3003260 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Multiple-antibiotic-resistance; Multidrug Efflux Pump; Sox-rob Regulon; Chromosomal Genes; Outer-membrane; Crystal-structure; Major Role; Expression; Mara; Activation
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Zeitschrift PLoS Biology
Quellenangaben Band: 23, Heft: 7, Seiten: 28, Artikelnummer: e3003260 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Deutsche Forschungsgemeinschaft
German Research Foundation
Bavarian State Ministry for Science and the Arts
Kempestiftelserna
Helmholtz Association's Initiative and Networking Fund through Opt4Bio