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.
Highlights
Bacterial foodborne diseases is a major public health concern worldwide. 9.4 million illnesses and 1,200 deaths are caused by foodborne bacterial pathogens every year in the United States (Kadariya et al, 2014)
The antibacterial activity of glabrol, licochalcone A, licochalcone C, and licochalcone E against methicillin-resistant S. aureus (MRSA) T144 and methicillin-sensitive S. aureus (MSSA) ATCC29213 was further confirmed by the Oxford cup method (Figure 2)
We found that glabrol, licochalcone A, licochalcone C, and licochalcone E displayed high efficiency against S. aureus, with low cell cytotoxicity to mammalian cells
Summary
Bacterial foodborne diseases is a major public health concern worldwide. 9.4 million illnesses and 1,200 deaths are caused by foodborne bacterial pathogens every year in the United States (Kadariya et al, 2014). Bacterial foodborne diseases is a major public health concern worldwide. 9.4 million illnesses and 1,200 deaths are caused by foodborne bacterial pathogens every year in the United States (Kadariya et al, 2014). Staphylococcus aureus is a highly virulent pathogen that causes food poisoning, skin and soft tissue infection, and sepsis (Claeys et al, 2019; Necidova et al, 2019; Packer et al, 2019). GRAPHICAL ABSTRACT | Glabrol isolated from licorice rapidly kill MRSA via the disruption of the membrane permeability and the proton motive force. The emergence and spread of multidrug resistant S. aureus isolates such as methicillin-resistant S. aureus (MRSA), further worsens the control of S. aureus associated infections. Effective strategies and new antibacterial agents against S. aureus are urgently needed (Aziz et al, 2015)
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