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The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa.
Zhao, Weining Cross, Ashley R Crowe-McAuliffe, Caillan Weigert-Munoz, Angela Csatary, Erika E Solinski, Amy E Krysiak, Joanna Goldberg, Joanna B Wilson, Daniel N
Zhao, Weining
Cross, Ashley R
Crowe-McAuliffe, Caillan
Weigert-Munoz, Angela
Csatary, Erika E
Solinski, Amy E
Krysiak, Joanna
Goldberg, Joanna B
Wilson, Daniel N
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2019-05-16
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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.
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Angew Chem Int Ed Engl. 2019;58(25):8581-8584. doi:10.1002/anie.201903472.
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en
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1521-3773
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Attribution-NonCommercial-ShareAlike 4.0 International