细菌药物耐受
Drug tolerance in bacteria
  
DOI:  10.13344/j.microbiol.china.180850
中文关键词:药物耐受,持留,耐药,抗生素
英文关键词:Drug tolerance, Persistence, Drug resistance, Antibiotics
基金项目:国家自然科学基金(31830002)
作者单位E-mail
吕亮东 1 复旦大学基础医学院 医学分子病毒学教育部/卫生部重点实验室 上海 200032 ld.lyu@fudan.edu.cn 
赵国屏 2 中国科学院上海植物生理生态研究所 中国科学院合成生物学重点实验室 上海 200032 gpzhao@sibs.ac.cn 
摘要点击次数: 351
全文下载次数: 411
中文摘要:
      细菌药物耐受(drug tolerance)是指在没有发生耐药突变的情况下细菌耐受抗生素杀菌的能力,表现为细菌群体难以或不能被杀菌型药物清除。细菌药物耐受的调控机制包括群体异质性和压力应答两种途径。药物耐受性的本质是细菌通过调控或遗传突变的方式改变生理代谢状态,从而抵制药物引起的细胞死亡途径。比如,处于缓慢生长或生长停滞生理状态的细菌往往能够抵抗药物的杀菌作用。临床研究发现细菌药物耐受是导致持续性感染疾病迁延难愈、复发率高的病原学机制之一。同时,研究证明耐受性的形成是细菌耐药性(drug resistance)产生的进化途径之一。因此,揭示细菌药物耐受的机制将有助于人们深入了解抗生素的杀菌机理,以及细菌耐药性形成的适应性进化机制,并为新型杀菌药物以及药物增效剂靶标的发现和抗生素合理使用策略的开发奠定理论基础。
英文摘要:
      Drug tolerance is the capacity of genetically susceptible bacteria to survive the killing by bactericidal antibiotics. At population level, drug tolerance can result in slow killing kinetics or failure of sterilization by antibiotic treatment. Drug tolerance can stem from phenotypic heterogeneity or from environmentally induced stress response at population level. While various genes and pathways were shown to be implicated in bacterial drug tolerance, it is becoming clear that the common mechanism underlies the survival of antibiotic-tolerant cells is the alteration of cellular growth or metabolic state achieved by either regulation or genetic mutation, which counteracts or diminishes the killing effect induced by the drug-target interaction. Increasing clinic evidence shows that drug tolerance is a causative reason account for the requirement of lengthy treatment and the high relapse rate observed in persistent infections. Importantly, recent studies demonstrated that drug tolerance could accelerate the emergency of drug-resistant mutants. Therefore, deciphering the molecular mechanisms of antibiotic tolerance may shed light on our understanding of antibiotic killing and the adaptive evolution of antibiotic resistance, and could facilitate the development of new intervention agents and therapeutic strategies.
吕亮东,赵国屏.细菌药物耐受[J].微生物学通报,2019,46(2):301~310
HTML  查看全文  查看/发表评论  下载PDF阅读器