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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase
Journal of the American Chemical Society, Volume 140, No. 5, Year 2018
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Description
Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings. © 2018 American Chemical Society.
Authors & Co-Authors
Steele, Andrew Duncan
United States, Atlanta
Emory University
Van-Tyne, Daria
United States, Boston
Harvard Medical School
Gilmore, Michael S.
United States, Boston
Harvard Medical School
Karanicolas, John
United States, Philadelphia
Fox Chase Cancer Center
Statistics
Citations: 57
Authors: 4
Affiliations: 7
Identifiers
Doi:
10.1021/jacs.7b11212
ISSN:
00027863