Unit for Drug Discovery, Department of Parasitology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil.
Curr Med Chem. 2014;21(15):1809-19. doi: 10.2174/0929867320666131119122520.
Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today a major burden in nosocomial disease control. The global trend shows an alarming increase of MRSA infections as well as multi-drug resistance (MDR). The problem is exacerbated by the fact that infections with community-associated (CA) MRSA strains showing increased virulence and fitness add to infections with multi-drug resistant hospital-associated (HA) MRSA. The toxicity of pathogens and limited effectiveness of available treatment have led to high mortality rates and vast expenses caused by prolonged hospitalization and usage of additional antibiotics. Recently approved drugs still have classical targets and upcoming resistance can be expected. In a new approach by targeting co-factor syntheses of bacteria, the drug target and the affected pathways are uncoupled. This novel strategy is based on the thought of a classical pro-drug which has to be metabolized before becoming toxic for the bacterium as a dysfunctional co-factor, named suicide drug. Ideally these metabolizing pathways are solely present in the bacterium and absent in the human host, such as vitamin biosyntheses. This mini-review discusses current ways of MRSA infection treatment using new approaches including suicide drugs targeting co-factor biosyntheses.
耐甲氧西林金黄色葡萄球菌（MRSA）引起的感染是当今医院感染控制的主要负担。全球趋势表明，MRSA 感染以及多药耐药（MDR）呈惊人的上升趋势。感染社区相关性（CA）MRSA 菌株的情况更加恶化，这些菌株具有更高的毒力和适应性，增加了多药耐药的医院相关性（HA）MRSA 的感染。病原体的毒性和现有治疗方法的有限效果导致高死亡率和因延长住院时间和使用额外抗生素而导致的巨大费用。最近批准的药物仍然具有经典的靶点，预计会出现新的耐药性。在一种通过靶向细菌辅助因子合成的新方法中，药物靶点和受影响的途径被分离。这种新策略基于经典前药的思想，前药必须在成为细菌的功能失调辅助因子（称为自杀药物）之前被代谢，才能对细菌产生毒性。理想情况下，这些代谢途径仅存在于细菌中，而不存在于人类宿主中，如维生素生物合成。这篇迷你综述讨论了使用包括靶向辅助因子生物合成的自杀药物在内的新方法治疗 MRSA 感染的当前方法。
