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The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa
Author(s) -
Zhao Weining,
Cross Ashley R.,
CroweMcAuliffe Caillan,
WeigertMunoz Angela,
Csatary Erika E.,
Solinski Amy E.,
Krysiak Joanna,
Goldberg Joanna B.,
Wilson Daniel N.,
Medina Eva,
Wuest William M.,
Sieber Stephan A.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201903472
Subject(s) - natural product , pseudomonas aeruginosa , bacteria , chemistry , antibiotics , proteome , microbiology and biotechnology , proteomics , computational biology , biology , biochemistry , gene , genetics
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.