Antibacterial Effect and Mode of Action of Flavonoids From Licorice Against Methicillin-Resistant Staphylococcus aureus

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.

Flavonoids as Potential anti-MRSA Agents through Modulation of PBP2a: A Computational and Experimental Study

“…Our inverse virtual screening applied in the present study proposes PBP2a to be the most possible target for the flavonoid class of compounds in our library. This in-silico suggestion is supported by a number of previous reports that illustrated flavonoids as possible modifiers of MRSA and other bacterial cell walls [18][19][20]. Further docking and molecular dynamic investigation not only confirmed the primary inverse virtual screening predictions but also revealed that some inactive derivatives can possibly modify the PBP2a allosteric site and hence, serve as adjuvants to reverse MRSA resistance toward β-lactams antibiotics (e.g., ampicillin 23).…”

“…Surprisingly, this immune active site has a weak point of being under the control of another allosteric site in the same protein, and thus, targeting such a lateral binding site can make MRSA susceptible to their routine antibiotics once again (Figure 7). Previous reports have suggested a number of flavonoids as possible modifiers of MRSA cell wall and cell membrane [18][19][20]. Moreover, several polyhydroxylated flavonoids have demonstrated considerable synergistic effect with β-lactams antibiotics [16,21], and PBP2a has been suggested as the possible target [22].…”

Potential Synergistic Action of Bioactive Compounds from Plant Extracts against Skin Infecting Microorganisms

“…Another antimicrobial agent targeting bacterial cell membranes are flavonoids including glabrol, licochalcone A, licochalcone C, and licochalcone E from licorice, the root and rhizome of Glycyrrhiza spp. They exhibit activity against methicillin-resistant S. aureus (MRSA), probably via binding to peptidoglycan, phosphatidylglycerol, and cardiolipin, dissipating proton move force, and increasing membrane permeability [67].…”

Systematic analysis of bacteriostatic mechanism of flavonoids using transcriptome and its therapeutic effect on vaginitis

“…Flavonoids are also well known for their antimicrobial capabilities. For example, it has been reported that glabrol, a flavonoid from licorice, displayed high efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in both in vivo and in vitro models [6]. A new class of modified flavonoids namely apigenin and quercetin was found to completely inhibit the growth of Listeria monocytogenes, Pseudomonas aeruginosa, and Aeromonas hydrophila [7].…”