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Antibacterial Effect and Mode of Action of Flavonoids From Licorice Against Methicillin-Resistant Staphylococcus
Shuai-Cheng Wu1,2,3, Zhi-Qiang Yang1, Fei Liu1
1Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Abstract:
Staphylococcus aureus is a bacterial pathogen that causes food poisoning, various infections, and sepsis. Effective strategies and new drugs are needed to control S. aureus associated infections due to the emergence and rapid dissemination of antibiotic resistance. In the present study, the antibacterial activity, potential mode of action, and applications of flavonoids from licorice were investigated. Here, we showed that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against methicillin-resistant Staphylococcus aureus (MRSA). Glabrol, licochalcone A, licochalcone C, and licochalcone E exhibited low cytotoxicity without hemolytic activity based on safety evaluation. Glabrol displayed rapid bactericidal activity with low levels of resistance development in vitro. Meanwhile, glabrol rapidly increased bacterial membrane permeability and dissipated the proton move force. Furthermore, we found that peptidoglycan, phosphatidylglycerol, and cardiolipin inhibited the antibacterial activity of glabrol. Molecular docking showed that glabrol binds to phosphatidylglycerol and cardiolipin through the formation of hydrogen bonds. Lastly, glabrol showed antibacterial activity against MRSA in both in vivo and in vitro models. Altogether, these results suggest that glabrol is a promising lead compound for the design of membrane-active antibacterial agents against MRSA and can be used as a disinfectant candidate as well.
Insights
Glabrol, a licorice flavonoid, effectively combats antibiotic-resistant Staphylococcus aureus (MRSA) by disrupting bacterial membranes. This compound shows promise as a new antibacterial agent and disinfectant.
Area of Science:
- Natural Products Chemistry
- Microbiology
- Pharmacology
Background:
- Staphylococcus aureus infections are a growing concern due to increasing antibiotic resistance.
- Novel therapeutic strategies are essential to combat infections caused by methicillin-resistant Staphylococcus aureus (MRSA).
Purpose of the Study:
- To investigate the antibacterial activity and mechanism of action of licorice flavonoids against MRSA.
- To evaluate the potential of glabrol as a lead compound for new antibacterial agents.
Main Methods:
- Screening of licorice flavonoids for antibacterial activity against MRSA.
- Cytotoxicity and hemolytic activity assays for safety evaluation.
- Investigation of glabrol's mode of action, including membrane permeability and proton motive force.
- Molecular docking to predict binding interactions.
- In vitro and in vivo efficacy studies.
Main Results:
- Glabrol, licochalcone A, C, and E demonstrated high efficacy against MRSA with low cytotoxicity.
- Glabrol exhibited rapid bactericidal activity and low resistance development in vitro.
- Glabrol increased bacterial membrane permeability and dissipated proton motive force.
- Molecular docking revealed hydrogen bonding between glabrol and phosphatidylglycerol/cardiolipin.
- Glabrol showed efficacy against MRSA in both in vitro and in vivo models.
Conclusions:
- Glabrol is a potent antibacterial agent against MRSA.
- Glabrol acts by disrupting bacterial membrane integrity.
- Glabrol is a promising candidate for developing novel membrane-active antibacterial agents and disinfectants.
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