Kim Yoonji, Choi Eunsil, Hwang Jihwan
Department of Microbiology, Pusan National University Busan, Republic of Korea.
Front Microbiol. 2016 Dec 21;7:2071. doi: 10.3389/fmicb.2016.02071. eCollection 2016.
Toxin-antitoxin (TA) systems, which consist of an intracellular toxin and its antidote (antitoxin), are encoded by ubiquitous genetic modules in prokaryotes. Commonly, the activity of a toxin is inhibited by its antitoxin under normal growth conditions. However, antitoxins are degraded in response to environmental stress, and toxins liberated from antitoxins consequently induce cell death or growth arrest. In free-living prokaryotes, TA systems are often present in large numbers and are considered to be associated with the adaptation of pathogenic bacteria or extremophiles to various unfavorable environments by shifting cells to a slow growth rate. Genomic analysis of the human pathogen H37Rv () revealed the presence of a large number of TA systems. Accordingly, we investigated five uncharacterized TA systems (Rv2019-Rv2018, Rv3697c-Rv3697A, Rv3180c-Rv3181c, Rv0299-Rv0298, and Rv3749c-Rv3750c) of . Among these, the expression of the Rv2019 toxin inhibited the growth of , and and this growth defect was recovered by the expression of the Rv2018 antitoxin. Interestingly, Rv3180c was toxic only in , whose toxicity was neutralized by Rv3181c antitoxin. and assays revealed the ribosomal RNA (rRNA) cleavage activity of the Rv2019 toxin. Moreover, mRNAs appeared to be substrates of Rv2019. Therefore, we concluded that the ribonuclease activity of the Rv2019 toxin triggers the growth defect in and that the Rv2018 antitoxin inhibits the ribonuclease activity of the Rv2019 toxin.
毒素-抗毒素（TA）系统由一种细胞内毒素及其解毒剂（抗毒素）组成，由原核生物中普遍存在的遗传模块编码。通常情况下，在正常生长条件下，毒素的活性会被其抗毒素抑制。然而，抗毒素会因环境压力而降解，从抗毒素中释放出来的毒素会因此诱导细胞死亡或生长停滞。在自由生活的原核生物中，TA系统通常大量存在，被认为与病原菌或嗜极菌通过将细胞转变为缓慢生长速率来适应各种不利环境有关。对人类病原体H37Rv（）的基因组分析揭示了大量TA系统的存在。因此，我们研究了的五个未表征的TA系统（Rv2019-Rv2018、Rv3697c-Rv3697A、Rv3180c-Rv3181c、Rv0299-Rv0298和Rv3749c-Rv3750c）。其中，Rv2019毒素的表达抑制了的生长，并且这种生长缺陷通过Rv2018抗毒素的表达得以恢复。有趣的是，Rv3180c仅在中具有毒性，其毒性被Rv3181c抗毒素中和。和实验揭示了Rv2019毒素的核糖体RNA（rRNA）切割活性。此外，mRNA似乎是Rv2019的底物。因此，我们得出结论，Rv2019毒素的核糖核酸酶活性触发了中的生长缺陷，并且Rv2018抗毒素抑制了Rv2019毒素 的核糖核酸酶活性。
