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Natural flavone hispidulin protects mice from Staphylococcus aureus pneumonia by inhibition of α-hemolysin production via targeting AgrA C .
- Source :
-
Microbiological research [Microbiol Res] 2022 Aug; Vol. 261, pp. 127071. Date of Electronic Publication: 2022 May 23. - Publication Year :
- 2022
-
Abstract
- The emergence of drug-resistant Staphylococcus aureus (S. aureus) has limited drug options for the clinical treatment of S. aureus infections. Considering recent reports, therapeutic strategies targeting bacterial virulence hold great promise, and alpha-hemolysin (encoded by hla), a critical virulence factor of S. aureus, plays a vital role during bacterial infection. Herein, we demonstrated that hispidulin effectively inhibited the hemolytic activity of S. aureus USA300 without suppressing bacterial growth, along with inhibiting hla transcription and expression in a dose-dependent manner. As heptamer formation is essential for hla-mediated invasion of cells, nevertheless, hispidulin did not affect the deoxycholate-induced oligomerization of hla, suggesting that hispidulin did not affect the protein activity of hla. In vitro assays illustrated that hispidulin bound to agrA <subscript>C</subscript> , a crucial protein in quorum sensing. Meanwhile, hispidulin alleviated A549 cell damage caused by S. aureus USA300 and reduced lactate dehydrogenase release. In vivo studies showed that hispidulin had a protective effect against pneumonia caused by S. aureus USA300 in mice. S. aureus did not develop resistance to hispidulin in the short term. Interestingly, our research indicated that hispidulin synergized with the antibacterial activity of cefoxitin. These results showed that hispidulin effectively inhibited α-hemolysin expression by inhibiting the agr quorum sensing of S. aureus. It has promise as an agent to treat S. aureus infection.<br /> (Copyright © 2022 Elsevier GmbH. All rights reserved.)
- Subjects :
- Animals
Bacterial Proteins metabolism
Hemolysin Proteins metabolism
Mice
Staphylococcus aureus
Bacterial Toxins metabolism
Flavones metabolism
Flavones pharmacology
Flavones therapeutic use
Methicillin-Resistant Staphylococcus aureus
Pneumonia, Staphylococcal drug therapy
Pneumonia, Staphylococcal microbiology
Pneumonia, Staphylococcal prevention & control
Staphylococcal Infections drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1618-0623
- Volume :
- 261
- Database :
- MEDLINE
- Journal :
- Microbiological research
- Publication Type :
- Academic Journal
- Accession number :
- 35660470
- Full Text :
- https://doi.org/10.1016/j.micres.2022.127071