Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Campus Bellvitge, University of Barcelona, Barcelona, Spain.
Department of Inorganic and Organic Chemistry, Faculty of Chemistry, University of Barcelona, 08907 Hospitalet, Barcelona, Spain.
J Antimicrob Chemother. 2018 Dec 1;73(12):3385-3390. doi: 10.1093/jac/dky366.
Staphylococcus aureus, including 'superbug' MRSA, is a major cause of nosocomial infections. In the European Union, up to 171 200 new nosocomial MRSA infections are acquired annually, and in the USA S. aureus causes more deaths than HIV/AIDS and tuberculosis combined. MRSA is also the first group of pathogens that infect the pulmonary tract in young patients with cystic fibrosis.
We describe two newly developed and synthesized colistin (polymyxin E)-inspired molecules.
A collection of several isolates of S. aureus [including MRSA and vancomycin-resistant S. aureus (VRSA)] was tested. To check the antimicrobial activity, we performed time-kill curves, growth curves, biofilm eradication, toxicity and isothermal titration calorimetry.
Both peptides showed high antimicrobial activities (MIC 4 mg/L) and low relative toxicities (selectivity index close to 23).
Successful production of polymyxin-scaffold molecules active against S. aureus, both MRSA and VRSA, opens up new approaches to the treatment of these complicated infections.
金黄色葡萄球菌（包括“超级细菌”耐甲氧西林金黄色葡萄球菌（MRSA））是医院获得性感染的主要原因。在欧盟，每年有多达 171200 例新的医院获得性 MRSA 感染，而在美国，金黄色葡萄球菌导致的死亡人数超过了艾滋病、结核病和艾滋病的总和。MRSA 也是感染年轻囊性纤维化患者肺部的第一批病原体。
我们描述了两种新开发和合成的粘菌素（多粘菌素 E）启发的分子。
我们测试了一组金黄色葡萄球菌（包括 MRSA 和万古霉素耐药金黄色葡萄球菌（VRSA））的分离株。为了检查抗菌活性，我们进行了时间杀伤曲线、生长曲线、生物膜清除、毒性和等温滴定量热法。
两种肽都表现出很高的抗菌活性（MIC 4mg/L）和较低的相对毒性（选择性指数接近 23）。
成功生产出针对金黄色葡萄球菌（包括 MRSA 和 VRSA）的多粘菌素支架分子，为治疗这些复杂感染开辟了新的途径。
