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The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa

The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity‐based protein profiling (AfBPP) in Gram‐positive and Gram‐negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellular P. aeruginosa in macrophages exposed to sub‐inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Angewandte Chemie International Edition Wiley

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References (29)

Publisher
Wiley
Copyright
© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1433-7851
eISSN
1521-3773
DOI
10.1002/anie.201903472
Publisher site
See Article on Publisher Site

Abstract

Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity‐based protein profiling (AfBPP) in Gram‐positive and Gram‐negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellular P. aeruginosa in macrophages exposed to sub‐inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.

Journal

Angewandte Chemie International EditionWiley

Published: May 17, 2020

Keywords: ; ; ; ;

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