@article {1297785,
	title = {Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase},
	journal = {J Am Chem Soc},
	volume = {140},
	number = {5},
	year = {2018},
	month = {2018 Feb 07},
	pages = {1774-1782},
	abstract = {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.},
	issn = {1520-5126},
	doi = {10.1021/jacs.7b11212},
	author = {Keohane, Colleen E and Steele, Andrew D and Fetzer, Christian and Khowsathit, Jittasak and Van Tyne, Daria and Moyni{\'e}, Lucile and Gilmore, Michael S and Karanicolas, John and Sieber, Stephan A and Wuest, William M}
}
