1. The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa
- Author
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Eva Medina, Joanna B. Goldberg, Ashley R. Cross, Weining Zhao, Amy E. Solinski, Joanna Krysiak, Stephan A. Sieber, Daniel N. Wilson, Caillan Crowe-McAuliffe, William M. Wuest, Angela Weigert‐Munoz, Erika E Csatary, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
- Subjects
medicine.drug_class ,natural products ,Mutant ,Antibiotics ,Microbial Sensitivity Tests ,010402 general chemistry ,medicine.disease_cause ,Proteomics ,01 natural sciences ,Catalysis ,antibiotics ,Article ,chemistry.chemical_compound ,Benzophenones ,Structure-Activity Relationship ,Fluoroquinolone Antibiotic ,chemical proteomics ,medicine ,Humans ,Norfloxacin ,Cells, Cultured ,Biological Products ,Natural product ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Pseudomonas aeruginosa ,Macrophages ,General Chemistry ,biology.organism_classification ,0104 chemical sciences ,Anti-Bacterial Agents ,virulence ,Biochemistry ,chemistry ,Bacteria ,medicine.drug - 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.
- Published
- 2019