Salam Akram M, Quave Cassandra L
Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
Center for the Study of Human Health, Emory University, Atlanta, Georgia, USA.
mSphere. 2018 Jan 17;3(1). doi: 10.1128/mSphere.00500-17. eCollection 2018 Jan-Feb.
Methicillin-resistant (MRSA) presents one of the most serious health concerns worldwide. The WHO labeled it as a "high-priority" pathogen in 2017, also citing the more recently emerged vancomycin-intermediate and -resistant strains. With the spread of antibiotic resistance due in large part to the selective pressure exerted by conventional antibiotics, the use of antivirulence strategies has been recurrently proposed as a promising therapeutic approach. In MRSA, virulence is chiefly controlled by quorum sensing (QS); inhibitors of QS are called quorum quenchers (QQ). In , the majority of QS components are coded for by the accessory gene regulator (Agr) system. Although much work has been done to develop QQs against MRSA, only a few studies have progressed to models. Those studies include both prophylactic and curative models of infection as well as combination treatments with antibiotic. For most, high efficacy is seen at attenuating MRSA virulence and pathogenicity, with some studies showing effects such as synergy with antibiotics and antibiotic resensitization. This minireview aims to summarize and derive conclusions from the literature on the efficacy of QQ agents in MRSA infection models. data are also summarized to provide sufficient background on the hits discussed. On the whole, the reported effects of the reviewed QQs against MRSA represent positive progress at this early stage in drug development. Follow-up studies that thoroughly examine and activity are needed to propel the field forward and set the stage for lead optimization.
耐甲氧西林金黄色葡萄球菌（MRSA）是全球最严重的健康问题之一。世界卫生组织在2017年将其列为“高度优先”病原体，还提到了最近出现的万古霉素中介和耐药菌株。由于传统抗生素施加的选择性压力，抗生素耐药性不断传播，因此，抗毒力策略作为一种有前景的治疗方法被反复提出。在MRSA中，毒力主要由群体感应（QS）控制；QS抑制剂被称为群体猝灭剂（QQ）。在MRSA中，大多数QS成分由辅助基因调节子（Agr）系统编码。尽管已经开展了许多针对MRSA开发QQ的工作，但只有少数研究进展到动物模型阶段。这些研究包括感染的预防和治疗模型以及与抗生素的联合治疗。对于大多数研究来说，在减弱MRSA毒力和致病性方面观察到了高效，一些研究显示出诸如与抗生素协同作用和使抗生素重新敏感等效果。本综述旨在总结关于QQ剂在MRSA感染模型中的疗效的文献并得出结论。还总结了相关数据，为所讨论的研究结果提供充分的背景信息。总体而言，所综述的QQ对MRSA的报道效果代表了药物开发早期阶段的积极进展。需要进行深入研究QQ体内和体外活性的后续研究，以推动该领域发展，并为先导化合物优化奠定基础。
