Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.
J Bacteriol. 2011 Mar;193(5):1122-30. doi: 10.1128/JB.01114-10. Epub 2010 Dec 23.
Type II chromosomal toxin-antitoxin (TA) modules consist of a pair of genes that encode two components: a stable toxin and a labile antitoxin interfering with the lethal action of the toxin through protein complex formation. Bioinformatic analysis of Streptococcus mutans UA159 genome identified a pair of linked genes encoding a MazEF-like TA. Our results show that S. mutans mazEF genes form a bicistronic operon that is cotranscribed from a σ70-like promoter. Overproduction of S. mutans MazF toxin had a toxic effect on S. mutans which can be neutralized by coexpression of its cognate antitoxin, S. mutans MazE. Although mazF expression inhibited cell growth, no cell lysis of S. mutans cultures was observed under the conditions tested. The MazEF TA is also functional in E. coli, where S. mutans MazF did not kill the cells but rather caused reversible cell growth arrest. Recombinant S. mutans MazE and MazF proteins were purified and were shown to interact with each other in vivo, confirming the nature of this TA as a type II addiction system. Our data indicate that MazF is a toxic nuclease arresting cell growth through the mechanism of RNA cleavage and that MazE inhibits the RNase activity of MazF by forming a complex. Our results suggest that the MazEF TA module might represent a cell growth modulator facilitating the persistence of S. mutans under the harsh conditions of the oral cavity.
II 型染色体毒素-抗毒素（TA）模块由一对基因组成，编码两种成分：一种稳定的毒素和一种不稳定的抗毒素，通过蛋白质复合物的形成干扰毒素的致命作用。对变形链球菌 UA159 基因组的生物信息学分析鉴定了一对编码 MazEF 样 TA 的连锁基因。我们的结果表明，变形链球菌 mazEF 基因形成一个双顺反子操纵子，由一个类似于 σ70 的启动子共同转录。过量表达变形链球菌 MazF 毒素对变形链球菌有毒性作用，其同源抗毒素变形链球菌 MazE 的共表达可以中和这种毒性作用。尽管 mazF 表达抑制了细胞生长，但在测试的条件下，未观察到变形链球菌培养物的细胞裂解。MazEF TA 在大肠杆菌中也是功能性的，其中变形链球菌 MazF 不会杀死细胞，而是导致细胞生长可逆性停滞。纯化的重组变形链球菌 MazE 和 MazF 蛋白相互作用，体内证实了这种 TA 作为 II 型成瘾系统的性质。我们的数据表明，MazF 是一种通过 RNA 切割机制阻止细胞生长的有毒核酸内切酶，而 MazE 通过形成复合物抑制 MazF 的核糖核酸酶活性。我们的结果表明，MazEF TA 模块可能代表一种细胞生长调节剂，有助于变形链球菌在口腔恶劣条件下的持续存在。
