• 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; Medina, Eva; et al. (Wiley-VCH, 2019-05-16)
      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.