The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa.
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Cross, Ashley R
Csatary, Erika E
Solinski, Amy E
Goldberg, Joanna B
Wilson, Daniel N
Wuest, William M
Sieber, Stephan A
MetadataShow full item record
AbstractNatural 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.
CitationAngew Chem Int Ed Engl. 2019;58(25):8581-8584. doi:10.1002/anie.201903472.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
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