原核生物Ⅶ型毒素-抗毒素系统研究进展

Progress of type Ⅶ toxin-antitoxin system in prokaryotes

摘要:

毒素-抗毒素（toxin-antitoxin，TA）系统是普遍存在于细菌、古细菌及原噬菌体中的遗传元件，通常由分别编码毒素和编码抗毒素的基因组成。毒素在细菌细胞中较为稳定，而抗毒素则容易被降解。大多数毒素为蛋白并具有酶的活性，通过影响蛋白质的翻译、DNA的复制等重要生命活动从而对细菌产生毒性，抑制细菌生长。抗毒素为蛋白质或非编码RNA，通过极其多样的方式，中和毒素的毒性。目前发现TA在调控质粒拷贝数、流产性感染、生物被膜的形成等过程中发挥着重要作用。随着研究的不断深入，新型TA不断被发现，极大地促进了我们对于TA的认识。目前TA已经扩展到I-Ⅷ型，本文总结了近期发现的新型TA，并重点介绍了最新发现的Ⅶ型TA及其特殊的中和机制。由于TA与病原微生物的致病性密切相关，因此，深入研究这些TA可以为耐药微生物的治疗提供新的靶点。

Abstract:

Toxin-antitoxin systems (TAs) are prevalent genetic elements in bacteria, archaea, and prophages, which are usually composed of a growth-inhibiting toxin and its cognate antitoxin. Toxins are stable in bacterial cells, while antitoxins are prone to be degraded by the ATP-dependent proteases. Most toxins are proteins and have enzyme activity, which inhibit bacterial growth by affecting important life activities such as protein translation and DNA replication. Antitoxins are either proteins or noncoding RNAs that neutralize the toxicity of toxins to bacteria in diverse ways. The available studies have demonstrated that TAs function as plasmid-stabilization elements, provide defense against phages, and promote biofilm formation. As the research deepens, increasing novel TAs have been discovered, which improves our understanding of TAs. At present, the classification of TAs has been extended to types Ⅰ-Ⅷ. This paper summarizes the recent discoveries of new TAs and focuses on the type Ⅶ TA in which the enzymatic antitoxin chemically modifies the toxin to neutralize it. Since TAs are closely associated with the pathogenicity of pathogenic microorganisms, in-depth study of these TAs can provide new targets for the treatment of drug-resistant microorganisms.