Theses and Dissertations at Montana State University (MSU)
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Item A review of plant-derived compounds and their potential for treating community-associated methicillin resistant Staphylococcus aureus(Montana State University - Bozeman, College of Letters & Science, 2013) Mead, Julia Suzanne; Chairperson, Graduate Committee: Jovanka Voyich-KaneMethicillin-resistant Staphylococcus aureus (MRSA) has been a global public health problem, especially in hospital settings, for more than fifty years. Within the last few decades, MRSA has undergone a shift in epidemiology, appearing more frequently in the community, and amongst people without traditional risk factors. Community-acquired (CA) MRSA strains contain a wide range of virulence factors and confer varying drug resistances. Infection with CA-MRSA can often lead to poor clinical outcomes, including death. Current treatments for severe infections are limited, and very few truly novel antibiotics are enrolled in late-phase clinical trials testing by the Food and Drug Administration. Vancomycin is currently the first choice of antibiotic for severe infections, however S. aureus strains with intermediate or full resistance to vancomycin have been reported since the early 2000's, thus the need for new antibiotics is urgent. This paper presents a literature review outlining the current body of knowledge regarding the use of plant-derived compounds and their activity against different strains of MRSA. Furthermore, the potential of these compounds for clinical use in treating MRSA infections will be assessed.Item 18-beta-glycyrrhetinic acid and methicillin resistant Staphylococcus aureus : from lytic activity to reduced pathogenesis(Montana State University - Bozeman, College of Agriculture, 2012) Long, Danyelle Renee; Chairperson, Graduate Committee: Jovanka Voyich-Kane; Julia Meade, Jay Hendricks, Michele E. Hardy and Jovanka M. Voyich were co-authors of the article, '18-beta-glycyrrhetinic acid inhibits MRSA survival and attenuates virulence gene expression' in the journal 'Antimicrobial agents and chemotherapy' which is contained within this thesis.Methicillin-resistant Staphylococcus aureus (MRSA) is Gram-positive pathogen known to cause severe disease in humans. MRSA's resistance to the beta-lactam class of antibiotics makes it an increasing healthcare concern. Over the last two decades there has been a rise in the incidence of community-associated MRSA, specifically pulsed-field gel electrophoresis type USA300 (known to cause severe skin and soft tissue infections). The development of drug therapies against MRSA infections that do not induce resistance and have efficacy against MRSA is a pressing matter. In this study, we investigate the potential of two components in licorice extracts, Glycyrrhizic acid (GA) and 18-beta-Glycyrrhetinic acid (GRA), as effective antimicrobials against MRSA. Using in vitro survival assays, we determined that GRA is directly bactericidal to MRSA. Using a murine model of skin and soft tissue infection, we discovered that topical treatment with GRA reduced severity of MRSA skin and soft tissue infections more rapidly than treatment with GA or a control. The increase in infection clearance was not due to a reduction in bacterial burden, but results indicate that GRA may decrease severity of the infection via an effect on the immune system. Treatment of an MRSA skin infection with GRA reduced expression of KC and G-CSF. To further investigate how GRA treatment led to a more rapid clearance of infection, we analyzed the expression of five S. aureus virulence genes (saeR, hla, RNAIII transcript, mecA, and sbi) after treatment with GRA or GA. GRA rapidly down-regulated four of the five virulence genes in vitro and all five virulence genes in vivo in the skin infection model. The data presented here shows that GRA is bactericidal, assists in decreasing the severity of MRSA infection via down-regulation of virulence genes, and can induce an altered immune response in the host.