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- Title
Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from Staphylococcus aureus.
- Authors
Zhou, Jia-Le; Chen, Hao-Han; Xu, Jian; Huang, Ming-Yu; Wang, Jun-Feng; Shen, Hao-Jie; Shen, Sheng-Xiang; Gao, Cheng-Xian; Qian, Chao-Dong
- 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.
- Subjects
NADH dehydrogenase; MYRICETIN; ENZYME kinetics; BIOCHEMICAL substrates; GENE expression; ENTEROTOXINS; MUPIROCIN
- Publication
Molecules, 2024, Vol 29, Issue 10, p2354
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules29102354