毒素-抗毒素系统及其典型模型研究进展  

Progress of Toxin-Antitoxin System and its Typical Models

作　　者：熊建伟 杜现礼 车永胜[2] 陈依军[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]军事医学科学院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《药物生物技术》2017年第5期421-425,共5页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.NSF83603001)

摘　　要：毒素-抗毒素系统广泛存在于细菌及古细菌基因组,毒素与抗毒素共表达形成稳定的复合物,毒素蛋白稳定而抗毒素不稳定。在压力条件下,被激活的毒素蛋白通过作用于旋转酶、mRNA、细胞膜等靶标,导致细菌生长持留或细胞死亡。大量关于毒素-抗毒素系统的报道,试图阐述病原菌本身的作用与毒素-抗毒素系统之间的关系。通过构建不同的试验模型及实验方法,探索所研究的毒素-抗毒素系统可能发挥的生理作用。目前研究已初步形成了一些理论模型,但是仍然存在许多的疑问。其中,以毒素-抗毒素系统为靶点,通过人工激活毒素-抗毒素系统,释放游离的毒素蛋白杀死病原菌或病毒,被认为是一种潜在的新型抗菌或抗病毒策略。研究毒素-抗毒素系统特征及其生物学功能,尤其是毒素-抗毒素参与的细菌持留模型和细菌程序性细胞死亡模型,有助于开发抗菌药及抗病毒药。Toxin-antitoxin systems are widely found in bacteria and archaea genomes,functioning to stabilize plasmids via post-segregation killing or benefit from the flexible cellular regulation under stress. Toxins are usually co-expressed with their cognate antitoxins and they form stable complexes under normal growth conditions. Toxins are stable while antitoxins are liable to be degraded.Stress-induced activation of toxins acts on cellular targets,such as gyrase,mRNA and cell membrane,causing bacterial persistence or death. The purpose of various reports about toxin-antitoxin systems is to explore the possible connection between toxin-antitoxin systems and pathogens. By building special experimental model,several models of toxin-antitoxin systems have been showed,but it is still doubtful. The most potential forward approach for activation of the toxin would be a drug that disrupts toxin-antitoxin complexes,and allows the free toxin to kill the bacteria or the pathogens. Research about the characteristics and biological functions of toxin-antitoxin systems contributes to the development of antibiotics and antiviral drugs,especially toxin-antitoxin systems involved in bacterial persistence model and bacterial programmed cell death model.

关 键 词：毒素-抗毒素系统 共表达 持留 靶标 程序性细胞死亡 抗病毒药 

分 类 号：Q57[生物学—生物化学]