Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in S. aureus strains has created a need for alternative therapies to treat disease. A component of the licorice root Glycyrrhiza spp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the in vitro and in vivo effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure of S. aureus to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including saeR and hla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of saeR and hla genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in S. aureus both in vitro and in vivo.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Anti-Bacterial Agents / pharmacology*
-
Bacterial Proteins / antagonists & inhibitors
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism
-
Bacterial Toxins / antagonists & inhibitors
-
Bacterial Toxins / genetics
-
Bacterial Toxins / metabolism
-
Female
-
Gene Expression Regulation, Bacterial / drug effects*
-
Glycyrrhetinic Acid / analogs & derivatives*
-
Glycyrrhetinic Acid / pharmacology
-
Hemolysin Proteins / antagonists & inhibitors
-
Hemolysin Proteins / genetics
-
Hemolysin Proteins / metabolism
-
Methicillin-Resistant Staphylococcus aureus / drug effects*
-
Methicillin-Resistant Staphylococcus aureus / genetics
-
Methicillin-Resistant Staphylococcus aureus / growth & development
-
Methicillin-Resistant Staphylococcus aureus / pathogenicity*
-
Mice
-
Microbial Sensitivity Tests
-
Skin / drug effects
-
Skin / microbiology
-
Skin / pathology
-
Soft Tissue Infections / drug therapy*
-
Soft Tissue Infections / microbiology
-
Soft Tissue Infections / pathology
-
Staphylococcal Skin Infections / drug therapy*
-
Staphylococcal Skin Infections / microbiology
-
Staphylococcal Skin Infections / pathology
-
Transcription Factors
-
Virulence
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
Bacterial Toxins
-
Hemolysin Proteins
-
SaeR protein, Staphylococcus aureus
-
Transcription Factors
-
staphylococcal alpha-toxin
-
18alpha-glycyrrhetinic acid
-
Glycyrrhetinic Acid