Anti-pathogenic activity of natural products from plants against MRSA

描述(由申请人提供)：结合药用植物应用的补充和替代医疗(CAM)实践在意大利南部很常见。大约三分之一的意大利植物学CAM疗法用于治疗皮肤病和伤口。由于植物产品的抗菌和抗炎特性，许多植物制剂的局部应用已被证明是有效的。此外，天然产物含有许多结构独特的化合物，其药用活性的潜力尚未得到充分开发。这项研究的目的是调查意大利植物疗法中使用的天然产品对常见病原体金黄色葡萄球菌的潜在作用机制。对耐甲氧西林金黄色葡萄球菌(MRSA)等耐药细菌的新型抗生素化合物的鉴定对全球范围内的医疗保健具有重要意义。这些机制的阐明也可以验证这些CAM疗法的疗效。来自微生物科学的新兴技术将纳入对来自意大利南部药用植物的天然产品的调查。这些工具将用于检查地中海CAM疗法对皮肤状况的抗菌潜力。这项研究的范围不仅限于对细菌生长影响的典型评估，还包括允许探索这些天然产品在调节微生物致病性方面所起作用的分析。群体感应(QS)抑制剂将被作为抗致病药物进行研究。在金黄色葡萄球菌中，QS或细胞间通讯是由辅助基因调节(AGR)系统介导的。AGR系统控制葡萄球菌毒素和细胞壁成分的产生，这些成分对生物膜基质的形成至关重要。在这项研究中，天然产物对QS介导的活动的影响将被量化。这将通过RNAIII的一种蛋白质产品--三角洲毒素的反相高效液相色谱定量来实现。通过体外测试塑料表面的粘附性，将研究对生物膜形成的抑制作用。葡萄球菌的生长抑制和哺乳动物的细胞毒性也将被调查。抗生素耐药性细菌对世界各地的医疗保健构成了重大威胁。迫切需要治疗耐药细菌感染的新药。在这项研究中，来自植物的天然产品将被分析作为新的抗生素药物的潜力。

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.