Khan Burhan A, Yeh Anthony J, Cheung Gordon Y C, Otto Michael
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories , 903 S. 4th St, 1/1110, Hamilton, MT 59840 , USA.
Expert Opin Investig Drugs. 2015 May;24(5):689-704. doi: 10.1517/13543784.2015.1019062. Epub 2015 Feb 23.
Antibiotic resistance is a serious global health concern for developed and developing nations. MRSA represents a particularly severe public health threat that is associated with high morbidity and mortality. The lack of novel antibiotics has led scientists to explore therapies targeting bacterial virulence mechanisms and virulence regulators, including those controlling cell-cell communication.
The authors discuss the role of quorum-sensing in Staphylococcus aureus infections and components of the system that are being targeted using novel investigational drugs. In particular, the authors examine the role of the accessory gene regulator (Agr) system in virulence regulation of S. aureus pathogenesis. Finally, the authors present and compare natural and synthetic compounds that have been found to interfere with Agr functionality.
There is a great need to develop new therapeutic methods to combat S. aureus infections. These include anti-virulence therapies that target key global regulators involved with the establishment and propagation of infection. Several molecules have been found to interfere with S. aureus virulence regulation, especially those targeting the Agr quorum-sensing signaling molecule. These preliminary findings warrant further investigation and validation, with the goal of refining a compound that has broad-spectrum inhibitory effects on most S. aureus strains and Agr subtypes.
抗生素耐药性是发达国家和发展中国家共同面临的严重全球健康问题。耐甲氧西林金黄色葡萄球菌(MRSA)是一种特别严重的公共卫生威胁,与高发病率和死亡率相关。新型抗生素的缺乏促使科学家探索针对细菌毒力机制和毒力调节因子的疗法,包括那些控制细胞间通讯的因子。
作者讨论了群体感应在金黄色葡萄球菌感染中的作用,以及正在使用新型研究药物靶向的该系统的组成部分。特别是,作者研究了辅助基因调节子(Agr)系统在金黄色葡萄球菌致病机制毒力调节中的作用。最后,作者展示并比较了已发现的干扰Agr功能的天然和合成化合物。
迫切需要开发新的治疗方法来对抗金黄色葡萄球菌感染。这些方法包括针对参与感染建立和传播的关键全局调节因子的抗毒力疗法。已发现几种分子可干扰金黄色葡萄球菌的毒力调节,尤其是那些靶向Agr群体感应信号分子的分子。这些初步发现值得进一步研究和验证,目标是优化一种对大多数金黄色葡萄球菌菌株和Agr亚型具有广谱抑制作用的化合物。