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Published on: September 8, 2021
Eriodictyol protects against Staphylococcus aureus-induced lung cell injury by inhibiting alpha-hemolysin expression
He Xuewen1, Ouyang Ping1, Yuan Zhongwei1
1College of Veterinary Medicine, Sichuan Agriculture University, Huimin Lu 211, Wenjiang, Chengdu, China.
Abstract:
Staphylococcus aureus (S. aureus) is a common pathogenic bacterium that causes various diseases in both humans and animals. With the increased prevalence of methicillin-resistant S. aureus, the therapeutic effects of commonly used antibiotics are limited against S. aureus infection. Novel treatment strategies and new antibiotics are needed urgently to address this concern. Many studies have shown that virulence factors secreted from S. aureus play vital roles in their pathogenic processes. Alpha-hemolysin (Hla), an important exotoxin in S. aureus, is one such virulence factor that increases sensitivity of multiple host cells to S. aureus resulting in various diseases. Eriodictyol is a flavonoid compound that exists in many fruits and vegetables. In this study, eriodictyol was demonstrated to inhibit the expression of Hla by hemolysis assays, western blotting, and RT-qPCR at the sub-minimal inhibitory concentration. In live/dead and cytotoxicity assays, the results showed that eriodictyol protected A549 cells against Hla-induced injury in a dose-dependent manner. The minimal inhibitory concentration of eriodictyol against S. aureus was 512 µg/mL. Eriodictyol can downregulate S. aureus Hla at both the expressional and transcriptional levels without affecting S. aureus growth. In addition, cell assays had proved that eriodictyol could protect A549 cells against Hla damage. Eriodictyol could therefore have the potential to treat S. aureus infection targeting Hla.
Insights
Eriodictyol, a plant flavonoid, effectively inhibits the Staphylococcus aureus alpha-hemolysin toxin without harming bacteria growth. This discovery offers a promising new strategy for treating S. aureus infections by targeting virulence factors.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Staphylococcus aureus (S. aureus) infections pose a significant health threat, exacerbated by antibiotic resistance.
- Alpha-hemolysin (Hla) is a key S. aureus virulence factor contributing to disease severity.
- Novel therapeutic strategies targeting virulence factors are crucial for combating S. aureus.
Purpose of the Study:
- To investigate the potential of eriodictyol, a flavonoid, in inhibiting S. aureus virulence factor Hla.
- To evaluate the protective effects of eriodictyol against Hla-induced host cell damage.
- To determine the impact of eriodictyol on S. aureus growth and Hla expression.
Main Methods:
- Hemolysis assays, western blotting, and RT-qPCR were used to assess Hla inhibition.
- Live/dead and cytotoxicity assays evaluated A549 cell protection against Hla.
- Minimal inhibitory concentration (MIC) assays determined eriodictyol's effect on bacterial growth.
Main Results:
- Eriodictyol significantly inhibited Hla expression at both transcriptional and protein levels at sub-MIC concentrations.
- Eriodictyol demonstrated dose-dependent protection of A549 cells from Hla-induced cytotoxicity.
- The MIC of eriodictyol against S. aureus was 512 µg/mL, indicating no significant impact on bacterial growth.
Conclusions:
- Eriodictyol effectively downregulates S. aureus alpha-hemolysin production without affecting bacterial viability.
- Eriodictyol exhibits cytoprotective properties against Hla-mediated host cell damage.
- Eriodictyol represents a potential therapeutic agent for S. aureus infections by targeting Hla.
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