A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection
Staphylococcus aureus, an important agent for lethal bacterial infections, can cause a broad spectrum of diseases in various host species. The emergence of multidrug-resistant and highly virulent strains has raised increasing concerns about the novel therapeutic strategies or agents available for tr...
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Frontiers Media S.A.
2020-07-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00330/full |
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author | Tingting Wang Tingting Wang Peng Zhang Hongfa Lv Xuming Deng Jianfeng Wang Jianfeng Wang |
author_facet | Tingting Wang Tingting Wang Peng Zhang Hongfa Lv Xuming Deng Jianfeng Wang Jianfeng Wang |
author_sort | Tingting Wang |
collection | DOAJ |
description | Staphylococcus aureus, an important agent for lethal bacterial infections, can cause a broad spectrum of diseases in various host species. The emergence of multidrug-resistant and highly virulent strains has raised increasing concerns about the novel therapeutic strategies or agents available for treating S. aureus infection. The critical role of Hla, an essential virulence determinant, in the pathogenicity of S. aureus renders this toxin an attractive target for effective therapeutic applications. Here, we have identified myricetin as an effective inhibitor of Hla that simultaneously inhibits Hla production and neutralizes Hla activity without affecting bacterial growth. Myricetin treatment reduced the oligomerization of Hla and Hla-mediated biofilm formation. The addition of myricetin to the coinfection system of host cells and S. aureus significantly decreased cell injury and downregulated the inflammatory response in cells. Furthermore, S. aureus-infected mice that received myricetin showed alleviated tissue damage in the lung. Our results indicated that myricetin inhibits S. aureus virulence by targeting Hla and downregulates the inflammatory response in host cells. Overall, in addition to traditional antibiotics with antibacterial activity, myricetin may represent a potential candidate, and strategy for S. aureus infection. |
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institution | Directory Open Access Journal |
issn | 2235-2988 |
language | English |
last_indexed | 2024-12-11T16:21:57Z |
publishDate | 2020-07-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cellular and Infection Microbiology |
spelling | doaj.art-98f4ce46c1524a8f9997840d6515b2832022-12-22T00:58:49ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-07-011010.3389/fcimb.2020.00330525386A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus InfectionTingting Wang0Tingting Wang1Peng Zhang2Hongfa Lv3Xuming Deng4Jianfeng Wang5Jianfeng Wang6Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Thoracic Surgery, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Thoracic Surgery, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, ChinaStaphylococcus aureus, an important agent for lethal bacterial infections, can cause a broad spectrum of diseases in various host species. The emergence of multidrug-resistant and highly virulent strains has raised increasing concerns about the novel therapeutic strategies or agents available for treating S. aureus infection. The critical role of Hla, an essential virulence determinant, in the pathogenicity of S. aureus renders this toxin an attractive target for effective therapeutic applications. Here, we have identified myricetin as an effective inhibitor of Hla that simultaneously inhibits Hla production and neutralizes Hla activity without affecting bacterial growth. Myricetin treatment reduced the oligomerization of Hla and Hla-mediated biofilm formation. The addition of myricetin to the coinfection system of host cells and S. aureus significantly decreased cell injury and downregulated the inflammatory response in cells. Furthermore, S. aureus-infected mice that received myricetin showed alleviated tissue damage in the lung. Our results indicated that myricetin inhibits S. aureus virulence by targeting Hla and downregulates the inflammatory response in host cells. Overall, in addition to traditional antibiotics with antibacterial activity, myricetin may represent a potential candidate, and strategy for S. aureus infection.https://www.frontiersin.org/article/10.3389/fcimb.2020.00330/fullmyricetinStaphylococcus aureusα-hemolysinanti-virulenceanti-infectioninflammation |
spellingShingle | Tingting Wang Tingting Wang Peng Zhang Hongfa Lv Xuming Deng Jianfeng Wang Jianfeng Wang A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection Frontiers in Cellular and Infection Microbiology myricetin Staphylococcus aureus α-hemolysin anti-virulence anti-infection inflammation |
title | A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection |
title_full | A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection |
title_fullStr | A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection |
title_full_unstemmed | A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection |
title_short | A Natural Dietary Flavone Myricetin as an α-Hemolysin Inhibitor for Controlling Staphylococcus aureus Infection |
title_sort | natural dietary flavone myricetin as an α hemolysin inhibitor for controlling staphylococcus aureus infection |
topic | myricetin Staphylococcus aureus α-hemolysin anti-virulence anti-infection inflammation |
url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00330/full |
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