喹诺酮类药物作用的生理和遗传的分子机制

The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones

氟喹诺酮类药物是目前使用最广泛的广谱抗生素,占据了全球抗生素类药物市场约18%的份额。其杀菌快速,而且具备大量的衍生物库,为药物更新换代提供了良好的基础。但这些衍生物在杀菌的速度、代谢过程中对氧需求、对蛋白合成的依赖性等方面的差异很大。从药物作用后细菌分子遗传层面的应答特征揭示各类衍生物的深层次作用机制,可以为寻找更有效的新喹诺酮类药物提供坚实基础。SOS应答、毒素-抗毒素系统,细菌程序性死亡、染色体片段化以及活性氧簇等新机制可能不同程度参与了喹诺酮类药物的杀菌过程。本文重点介绍喹诺酮作用的"二步特征"。该特征的引入有助于理解不同喹诺酮类药物的杀菌特征,也有助于开发新的喹诺酮类药物。

The fluoroquinolones are the most widely used broad-spectrum antibiotics,accounting for 18% of global antibacterial market share.They can kill bacteria rapidly with variety of derivatives available.Different quinolones vary significantly in rate and spectrum of killing,oxygen requirement for metabolism and reliance upon protein synthesis.Further understanding the sophisticated mechanisms of action of this important antibiotic family based on the molecular genetic response of bacteria can facilitate the discovery of better quinolone derivatives.Factors such as SOS response,bacterial toxin-antitoxin system,programmed death,chromosome fragmentation and reactive oxygen have been implicated in the action to some extent.＂Two steps characteristic＂ of quinolones killing is also emphasized,which might inspire future better quinolones modification.