Faculty of Life Sciences and Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester, UK.
Crit Rev Biochem Mol Biol. 2011 Oct;46(5):386-408. doi: 10.3109/10409238.2011.600437. Epub 2011 Aug 5.
Genes for toxin-antitoxin (TA) complexes are widespread in prokaryote genomes, and species frequently possess tens of plasmid and chromosomal TA loci. The complexes are categorized into three types based on genetic organization and mode of action. The toxins universally are proteins directed against specific intracellular targets, whereas the antitoxins are either proteins or small RNAs that neutralize the toxin or inhibit toxin synthesis. Within the three types of complex, there has been extensive evolutionary shuffling of toxin and antitoxin genes leading to considerable diversity in TA combinations. The intracellular targets of the protein toxins similarly are varied. Numerous toxins, many of which are sequence-specific endoribonucleases, dampen protein synthesis levels in response to a range of stress and nutritional stimuli. Key resources are conserved as a result ensuring the survival of individual cells and therefore the bacterial population. The toxin effects generally are transient and reversible permitting a set of dynamic, tunable responses that reflect environmental conditions. Moreover, by harboring multiple toxins that intercede in protein synthesis in response to different physiological cues, bacteria potentially sense an assortment of metabolic perturbations that are channeled through different TA complexes. Other toxins interfere with the action of topoisomersases, cell wall assembly, or cytoskeletal structures. TAs also play important roles in bacterial persistence, biofilm formation and multidrug tolerance, and have considerable potential both as new components of the genetic toolbox and as targets for novel antibacterial drugs.
毒素-抗毒素（TA）复合体基因广泛存在于原核生物基因组中，许多物种拥有数十个质粒和染色体 TA 基因座。这些复合体根据遗传组织和作用模式分为三种类型。毒素通常是针对特定细胞内靶标的蛋白质，而抗毒素可以是蛋白质或小 RNA，它们可以中和毒素或抑制毒素合成。在这三种类型的复合体中，毒素和抗毒素基因发生了广泛的进化重排，导致 TA 组合具有很大的多样性。蛋白质毒素的细胞内靶标也多种多样。许多毒素是序列特异性内切核糖核酸酶，它们根据一系列应激和营养刺激来调节蛋白质合成水平。由于关键资源得到了保护，因此确保了单个细胞和细菌种群的存活。毒素的作用通常是短暂和可逆的，从而允许产生一系列动态的、可调节的反应，以反映环境条件。此外，通过携带多种毒素，这些毒素可以针对不同的生理信号干预蛋白质合成，细菌有可能感知到一系列代谢紊乱，这些紊乱通过不同的 TA 复合体进行传递。其他毒素会干扰拓扑异构酶、细胞壁组装或细胞骨架结构的功能。TA 还在细菌的持久性、生物膜形成和多药耐药性中发挥重要作用，它们具有作为遗传工具箱的新组件以及作为新型抗菌药物靶点的巨大潜力。
