细菌毒素-抗毒素系统在噬菌体流产感染中的作用

The role of bacterial toxin-antitoxin systems in phage abortive infections

摘要:

细菌常受到数量众多的噬菌体感染，宿主细菌在和噬菌体竞赛中进化出多样化的分子策略，流产感染(abortive infection,Abi)是其中之一。毒素-抗毒素系统(toxin-antitoxin system,TA)会在细菌受到压力胁迫时表达并介导细菌的低代谢甚至休眠，还能直接减少子代噬菌体形成。此外，部分毒素序列和结构与Cas蛋白高度同源，噬菌体甚至会编码抗毒素类似物来阻遏对应毒素的活性。这表明流产感染中细菌死亡过程导致的噬菌体感染失败与TA功能高度重合，TA可能是噬菌体侵染宿主的主要阻力和防御力量之一。文中基于TA系统的分类和功能，对参与噬菌体流产感染的TA系统进行了综述，并预测具有流产功能的TA系统和其在抗生素开发和疾病治疗中的应用前景。这有助于认识细菌-噬菌体相互作用，并指导噬菌体治疗和合成生物学。

Abstract:

Bacteria are often infected by large numbers of phages, and host bacteria have evolved diverse molecular strategies in the race with phages, with abortive infection (Abi) being one of them. The toxin-antitoxin system (TA) is expressed in response to bacterial stress, mediating hypometabolism and even dormancy, as well as directly reducing the formation of offspring phages. In addition, some of the toxins' sequences and structures are highly homologous to Cas, and phages even encode antitoxin analogs to block the activity of the corresponding toxins. This suggests that the failure of phage infection due to bacterial death in abortive infections is highly compatible with TA function, whereas TA may be one of the main resistance and defense forces for phage infestation of the host. This review summarized the TA systems involved in phage abortive infections based on classification and function. Moreover, TA systems with abortive functions and future use in antibiotic development and disease treatment were predicted. This will facilitate the understanding of bacterial-phage interactions as well as phage therapy and related synthetic biology research.