학술논문
Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from Staphylococcus aureus .
Document Type
Academic Journal
Author
Zhou JL; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Chen HH; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Xu J; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Huang MY; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Wang JF; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Shen HJ; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Shen SX; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Gao CX; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.; Qian CD; College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus . The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus .
Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50 ) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus . In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner.
Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.
Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC
Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.