Anti-pathogenic activity of natural products from plants against MRSA

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DESCRIPTION (provided by applicant): Complementary and alternative medical (CAM) practices that incorporate the application of medicinal plants are commonplace in southern Italy. Approximately one-third of Italian botanical CAM therapies are used to treat skin disorders and wounds. The topical application of many botanical preparations has proven effective due to the antimicrobial and anti-inflammatory properties of plant products. Furthermore, natural products hold a reservoir of many structurally unique compounds and the potential for their medicinal activity has not yet been fully explored. The aim of this study is to investigate natural products used in Italian botanical therapies for their underlying mechanisms of action against the common pathogen, Staphylococcus aureus. The identification of novel antibiotic compounds for drug resistant bacteria such as methicillin resistant S. aureus (MRSA) is important to healthcare on a global scale. The elucidation of such mechanisms could also validate the efficacy of these CAM therapies. Emerging technologies from microbiological science will be incorporated into the investigation of natural products derived from south Italian medicinal plants. These tools will be used in the examination of the antibacterial potential of Mediterranean CAM therapies for skin conditions. The scope of the study is not limited to the typical assessment of impact on bacterial growth, but also includes assays that allow for exploration of the role that these natural products play in mediating microbial pathogenicity. Quorum-sensing (QS) inhibitors will be investigated as anti-pathogenic drugs. QS, or cell-cell communication, is mediated by the accessory gene regulator (agr) system in S. aureus. The agr system controls the production of staphylococcal toxins and cell-wall constituents important to the formation of biofilm matrices. In this study, the impact of natural products on QS-mediated activities will be quantified. This will be accomplished through RP-HPLC quantification of delta-toxin, a protein product of RNAIII. Inhibition of biofilm formation will be investigated via in vitro tests for adherence to plastic surfaces. Staphylococcal growth-inhibition and mammalian cytotoxicity will also be investigated. Antibiotic resistant bacteria pose a significant threat to healthcare worldwide. New drugs for the treatment of drug resistant bacterial infections are urgently needed. In this study, natural products from plants will be analyzed for their potential as new antibiotic drugs.