title: 18β-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression.
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.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA.
authors.forename: Danyelle R
authors.initials: DR
authors.lastname: Long
authors.forename: Julia
authors.initials: J
authors.lastname: Mead
authors.forename: Jay M
authors.initials: JM
authors.lastname: Hendricks
authors.forename: Michele E
authors.initials: ME
authors.lastname: Hardy
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006460:Hemolysin Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D051379:Mice; D008826:Microbial Sensitivity Tests; D012867:Skin / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D014157:Transcription Factors; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; C021091:staphylococcal alpha-toxin; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid