Proteomics

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The natural product elegaphenone potentiates antibiotic effects against Pseudomonas aeruginosa


ABSTRACT: Natural products represent a rich source for antibiotics addressing versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we select 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 revealed unique insights into the mode of action. Elegaphenone enhanced the killing of intracellular P. aeruginosa in macrophages exposed to sub-inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Enterococcus faecalis  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Weining Zhao  

LAB HEAD: Stephan Axel Sieber

PROVIDER: PXD010476 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa.

Zhao Weining W   Cross Ashley R AR   Crowe-McAuliffe Caillan C   Weigert-Munoz Angela A   Csatary Erika E EE   Solinski Amy E AE   Krysiak Joanna J   Goldberg Joanna B JB   Wilson Daniel N DN   Medina Eva E   Wuest William M WM   Sieber Stephan A SA  

Angewandte Chemie (International ed. in English) 20190516 25


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 scaffo  ...[more]

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