Molecular Microbiology Research Laboratory, Institute of Pharmaceutical Sciences, King's College London, London, UK.
Br J Pharmacol. 2012 Feb;165(4):845-57. doi: 10.1111/j.1476-5381.2011.01643.x.
The discovery of novel classes of antibiotics has slowed dramatically. This has occurred during a time when the appearance of resistant strains of bacteria has shown a substantial increase. Concern is therefore mounting over our ability to continue to treat infections in an effective manner using the antibiotics that are currently available. While ongoing efforts to discover new antibiotics are important, these must be coupled with strategies that aim to maintain as far as possible the spectrum of activity of existing antibiotics. In many instances, the resistance to antibiotics exhibited by bacteria in chronic infections is mediated not by direct resistance mechanisms, but by the adoption of modes of growth that confer reduced susceptibility. These include the formation of biofilms and the occurrence of subpopulations of 'persister' cells. As our understanding of these processes has increased, a number of new potential drug targets have been revealed. Here, advances in our ability to disrupt these systems that confer reduced susceptibility, and in turn increase the efficacy of antibiotic therapy, are discussed.
新型抗生素的发现速度已经大大减缓。而在这段时间里，细菌耐药菌株的出现率显著增加。因此，人们越来越担心我们是否有能力继续使用现有的抗生素有效地治疗感染。虽然发现新抗生素的持续努力很重要，但这些努力必须与旨在尽可能维持现有抗生素的活性谱的策略相结合。在许多情况下，慢性感染中细菌对抗生素的耐药性不是由直接耐药机制介导的，而是通过采用降低敏感性的生长方式来实现的。这些方式包括生物膜的形成和“持久细胞”亚群的出现。随着我们对这些过程的了解不断增加，已经揭示了一些新的潜在药物靶点。在这里，讨论了破坏这些降低敏感性的系统并提高抗生素治疗效果的能力的进展。
