Deter Heather S, Jensen Roderick V, Mather William H, Butzin Nicholas C
Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435, USA.
Center for Soft Matter and Biological Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0435, USA.
Toxins (Basel). 2017 Jul 4;9(7):211. doi: 10.3390/toxins9070211.
Toxin-antitoxin (TA) systems are key regulators of bacterial persistence, a multidrug-tolerant state found in bacterial species that is a major contributing factor to the growing human health crisis of antibiotic resistance. Type II TA systems consist of two proteins, a toxin and an antitoxin; the toxin is neutralized when they form a complex. The ratio of antitoxin to toxin is significantly greater than 1.0 in the susceptible population (non-persister state), but this ratio is expected to become smaller during persistence. Analysis of multiple datasets (RNA-seq, ribosome profiling) and results from translation initiation rate calculators reveal multiple mechanisms that ensure a high antitoxin-to-toxin ratio in the non-persister state. The regulation mechanisms include both translational and transcriptional regulation. We classified type II TA systems into four distinct classes based on the mechanism of differential protein production between toxin and antitoxin. We find that the most common regulation mechanism is translational regulation. This classification scheme further refines our understanding of one of the fundamental mechanisms underlying bacterial persistence, especially regarding maintenance of the antitoxin-to-toxin ratio.
毒素-抗毒素（TA）系统是细菌持留性的关键调节因子，细菌持留性是在细菌物种中发现的一种多药耐受状态，是导致抗生素耐药性这一日益严重的人类健康危机的主要因素。II型TA系统由两种蛋白质组成，一种毒素和一种抗毒素；当它们形成复合物时，毒素被中和。在易感群体（非持留状态）中，抗毒素与毒素的比例显著大于1.0，但在持留期间，这个比例预计会变小。对多个数据集（RNA测序、核糖体谱分析）的分析以及翻译起始率计算器的结果揭示了多种机制，这些机制确保了在非持留状态下抗毒素与毒素的高比例。调节机制包括翻译调节和转录调节。我们根据毒素和抗毒素之间蛋白质产生差异的机制，将II型TA系统分为四个不同的类别。我们发现最常见的调节机制是翻译调节。这种分类方案进一步完善了我们对细菌持留性潜在基本机制之一的理解，特别是关于抗毒素与毒素比例的维持。
