Natural Flavones from Morus alba against Methicillin-Resistant Staphylococcus aureus via Targeting the Proton Motive Force and Membrane Permeability.
J Agric Food Chem
; 67(36): 10222-10234, 2019 Sep 11.
Article
em En
| MEDLINE
| ID: mdl-31385700
ABSTRACT
The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA-associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency in killing diverse MRSA isolates. On the basis of structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase the membrane permeability and to dissipate the proton motive force. Meanwhile, mechanistic studies further showed that kuwanon G displayed rapid bactericidal activity in vitrowith difficulty in developing drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interactions. Additionally, kuwanon G promoted wound healing in a mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA-associated infections through disrupting the proton motive force and membrane permeability.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções Estafilocócicas
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Extratos Vegetais
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Morus
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Flavonas
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Staphylococcus aureus Resistente à Meticilina
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Antibacterianos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China