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):

ORGANISM(S): Enterococcus Faecalis (streptococcus Faecalis)

SUBMITTER: Weining Zhao  

LAB HEAD: Stephan Axel Sieber

PROVIDER: PXD010476 | Pride | 2021-09-08

REPOSITORIES: Pride