Smith Peter A, Romesberg Floyd E
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Nat Chem Biol. 2007 Sep;3(9):549-56. doi: 10.1038/nchembio.2007.27.
Antibiotics have revolutionized the treatment of infectious disease but have also rapidly selected for the emergence of resistant pathogens. Traditional methods of antibiotic discovery have failed to keep pace with the evolution of this resistance, which suggests that new strategies to combat bacterial infections may be required. An improved understanding of bacterial stress responses and evolution suggests that in some circumstances, the ability of bacteria to survive antibiotic therapy either by transiently tolerating antibiotics or by evolving resistance requires specific biochemical processes that may themselves be subject to intervention. Inhibiting these processes may prolong the efficacy of current antibiotics and provide an alternative to escalating the current arms race between antibiotics and bacterial resistance. Though these approaches are not clinically validated and will certainly face their own set of challenges, their potential to protect our ever-shrinking arsenal of antibiotics merits their investigation. This Review summarizes the early efforts toward this goal.
抗生素彻底改变了传染病的治疗方式，但也迅速导致了耐药病原体的出现。传统的抗生素发现方法未能跟上这种耐药性的演变，这表明可能需要新的策略来对抗细菌感染。对细菌应激反应和进化的深入理解表明，在某些情况下，细菌通过短暂耐受抗生素或进化出耐药性来在抗生素治疗中存活的能力需要特定的生化过程，而这些过程本身可能易于受到干预。抑制这些过程可能会延长现有抗生素的疗效，并为缓和当前抗生素与细菌耐药性之间不断升级的军备竞赛提供一种替代方法。尽管这些方法尚未经过临床验证，而且肯定会面临自身的一系列挑战，但它们保护我们日益减少的抗生素库的潜力值得研究。本综述总结了为实现这一目标所做的早期努力。
