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Enhanced NADH Metabolism Involves Colistin-Induced Killing of Bacillus subtilis and Paenibacillus polymyxa

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Francesc Rabanal Anglada
Molecules 2019, 24(3), 387;
Received: 4 December 2018 / Revised: 8 January 2019 / Accepted: 22 January 2019 / Published: 22 January 2019
(This article belongs to the Special Issue Polymyxins)
PDF [2118 KB, uploaded 27 January 2019]


The commonly believed mechanism of colistin against Gram-negative bacteria is to cause cell membrane lysis, whereas the mechanism of colistin against Gram-positive bacteria is extremely fragmented. In this study, we found that colistin treatment on Bacillus subtilis WB800, Paenibacillus polymyxa C12 and Paenibacillus polymyxa ATCC842 enhances not only the activities of α-ketoglutaric dehydrogenase and malate dehydrogenase in tricarboxylic acid (TCA) cycle, but also the relative expression levels of their encoding genes. Additionally, the oxaloacetate concentration also increases. Interestingly, the analysis of the relative expression of genes specific for respiratory chain showed that colistin treatment stimulates the respiratory chain in Gram-positive bacteria. Accordingly, the NAD+/NADH ratio increases and the oxidative level is then boosted up. As a result, the intensive oxidative damages are induced in Gram-positive bacteria and cells are killed. Notably, both rotenone and oligomycin, respectively, inhibiting NADH dehydrogenase and phosphorylation on respiratory chain can downgrade oxidative stress formation, thus alleviating the colistin-induced killing of Gram-positive cells. Besides, thiourea-based scavenging for reactive oxygen species also rescues the colistin-subjected cells. These data collectively demonstrate that colistin stimulates both TCA cycle and respiratory chain in Gram-positive bacteria, leading to the enhancement of NADH metabolism and resulting in the generation of oxidative damages in Gram-positive cells. Our studies provide a better understanding of antibacterial mechanism of colistin against Gram-positive bacteria, which is important for knowledge on bacterial resistance to colistin happening via the inhibition of respiratory chain and manipulation of its production. View Full-Text
Keywords: colistin; Gram-positive bacteria; oxidative stress; TCA cycle; respiratory chain colistin; Gram-positive bacteria; oxidative stress; TCA cycle; respiratory chain

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Yu, Z.; Zhu, Y.; Fu, J.; Qiu, J.; Yin, J. Enhanced NADH Metabolism Involves Colistin-Induced Killing of Bacillus subtilis and Paenibacillus polymyxa. Molecules 2019, 24, 387.

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