Antimicrobial mechanism of resveratrol-trans-dihydrodimer produced from peroxidase-catalyzed oxidation of resveratrol

作者：Mora Pale Mauricio; Bhan Namita; Masuko Sayaka; James Paul; Wood Julia; McCallum Scott; Linhardt Robert J; Dordick Jonathan S^*; Koffas Mattheos A G

来源：Biotechnology and Bioengineering, 2015, 112(12): 2417-2428.

DOI：10.1002/bit.25686

• resveratrol
• peroxidase
• antimicrobial
• disrupted membrane potential
• DNA gyrase inhibition

Plant polyphenols are known to have varying antimicrobial potencies, including direct antibacterial activity, synergism with antibiotics and suppression of bacterial virulence. We performed the in vitro oligomerization of resveratrol catalyzed by soybean peroxidase, and the two isomers (resveratrol-trans-dihydrodimer and pallidol) produced were tested for antimicrobial activity. The resveratrol-trans-dihydrodimer displayed antimicrobial activity against the Gram-positive bacteria Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus (minimum inhibitory concentration (MIC)=15.0, 125, and 62.0M, respectively) and against Gram-negative Escherichia coli (MIC=123M, upon addition of the efflux pump inhibitor Phe-Arg--naphthylamide). In contrast, pallidol had no observable antimicrobial activity against all tested strains. Transcriptomic analysis implied downregulation of ABC transporters, genes involved in cell division and DNA binding proteins. Flow cytometric analysis of treated cells revealed a rapid collapse in membrane potential and a substantial decrease in total DNA content. The active dimer showed >90% inhibition of DNA gyrase activity, in vitro, by blocking the ATP binding site of the enzyme. We thus propose that the resveratrol-trans-dihydrodimer acts to: (1) disrupt membrane potential; and (2) inhibit DNA synthesis. In summary, we introduce the mechanisms of action and the initial evaluation of an active bactericide, and a platform for the development of polyphenolic antimicrobials. Biotechnol. Bioeng. 2015;112: 2417-2428.

• 出版日期2015-12