Giglio Krista M, Keohane Colleen E, Stodghill Paul V, Steele Andrew D, Fetzer Christian, Sieber Stephan A, Filiatrault Melanie J, Wuest William M
Emerging Pests and Pathogens Research, United States Department of Agriculture, Agricultural Research Service, 538 Tower Road , Ithaca , New York 14853 , United States.
Department of Chemistry , Emory University , 1515 Dickey Drive , Atlanta , Georgia 30322 , United States.
ACS Infect Dis. 2018 Aug 10;4(8):1179-1187. doi: 10.1021/acsinfecdis.8b00041. Epub 2018 Jun 5.
Promysalin, a secondary metabolite produced by P. putida RW10S1, is a narrow-spectrum antibiotic that targets P. aeruginosa over other Pseudomonas spp. P. putida KT2440, a nonproducing strain, displays increased swarming motility and decreased pyoverdine production in the presence of exogenous promysalin. Herein, proteomic and transcriptomic experiments were used to provide insight about how promysalin elicits responses in PPKT2440 and rationalize its species selectivity. RNA-sequencing results suggest that promysalin affects PPKT2440 by (1) increasing swarming in a flagella-independent manner; (2) causing cells to behave as if they were experiencing an iron-deficient environment, and (3) shifting metabolism away from glucose conversion to pyruvate via the Entner-Doudoroff pathway. These findings highlight nature's ability to develop small molecules with specific targets, resulting in exquisite selectivity.
普罗米沙林是恶臭假单胞菌RW10S1产生的一种次级代谢产物,是一种窄谱抗生素,相较于其他假单胞菌属,它对铜绿假单胞菌具有靶向作用。恶臭假单胞菌KT2440是一种不产生普罗米沙林的菌株,在存在外源性普罗米沙林的情况下,它表现出群体游动能力增强且绿脓菌素产量降低。在此,蛋白质组学和转录组学实验被用于深入了解普罗米沙林如何在恶臭假单胞菌KT2440中引发反应,并阐明其物种选择性的原理。RNA测序结果表明,普罗米沙林通过以下方式影响恶臭假单胞菌KT2440:(1)以不依赖鞭毛的方式增加群体游动;(2)使细胞表现得好像它们正处于缺铁环境中;(3)将代谢从通过恩特纳-杜德洛夫途径将葡萄糖转化为丙酮酸的过程中转移出来。这些发现凸显了自然界开发具有特定靶点的小分子的能力,从而产生了精确的选择性。