近年来研究表明，细菌染色体编码的毒素抗毒素系统参与不良条件下细菌生长调控，使细菌在应激条件下进入休眠状态而得到保护。典型的毒素抗毒素系统包含共表达的一对基因分别表达不稳定的抗毒素和稳定的毒素。目前研究得最深入的是E.coli染色体上的 mazE-mazF系统。在正常状态下，毒素MazF与抗毒素MazE结合形成复合体。MazE和MazE-MazF复合体都能与MazEF启动子结合，自反馈抑制基因表达。在氨基酸缺乏的情况下,警报信号因子ppGpp合成增加，抑制了MazE-MazF基因的表达，MazE被蛋白酶降解，MazF得以发挥核糖核酸内切酶活性，通过降解mRNA抑制蛋白质合成，从而抑制细菌生长。 结核分枝杆菌（Mycobacterium tuberculosis）基因组上存在多个mazF的同源基因。我们通过计算机序列分析，发现其中一个mazF同源基因Rv1991c与其上游一个开放读框Rv1991a可能组成一对典型的毒素-抗毒素系统。在E.coli和耻垢分枝杆菌中诱导表达Rv1991c均能导致细菌生长抑制；而在表达Rv1991c的同时表达Rv1991a能使细菌生长正常，证明了Rv1991c和Rv1991a是一对毒素和抗毒素。经原核表达纯化获得Rv1991c和Rv1991a蛋白。两者经共同孵育后，在非变性电泳中可检测到复合体的条带。将复合体条带切下来进行变性电泳，显示出2条分别和Rv1991c和Rv1991a蛋白一样大小的条带。这些结果表明Rv1991a通过与Rv1991c形成蛋白复合体的形式来抑制Rv1991c的毒性。通过进一步体外实验发现，Rv1991c蛋白能切割人工合成的RNA底物，而加入Rv1991a蛋白能抑制该活性。我们还发现了Rv1991a的上游存在着一个99bp的有启动子活性的区域。Rv1991a蛋白和Rv1991a-Rv1991c复合体均能与上游启动子区DNA结合，这暗示了rv1991a -rv1991c系统存在可能的自反馈调控方式。通过定点突变Rv1991a N端高度保守的氨基酸残基（S25和R26）能使Rv1991a丧失结合启动子区DNA的能力。以上结果显示结核杆菌基因组上的rv1991a -rv1991c 操纵子是一个典型的毒素抗毒素系统，其中Rv1991c是毒素蛋白，通过发挥其RNA内切酶活性来抑制细菌的生长；而Rv1991a蛋白是抗毒素，能与毒素直接形成复合体，从而中和Rv1991c的毒性。抗毒素和毒素-抗毒素复合体都能通过抗毒素N端与其上游的启动子区结合。但是rv1991a -rv1991c毒素-抗毒素系统在应激条件下的表达调控及其生理作用还有待深入研究。

The chromosomal toxin-antitoxin (TA) systems are proposed to be involved in the bacterial cell growth control under the stress conditions, allowing cells to enter a dormant state as a protection against severe condition. A typical TA system consists of a pair of genes encoding an unstable antitoxin and a stable toxin respectively. The mazE-mazF system is a well-known TA system on Escherichia coli chromosome. The mazF homologue genes have been identified in Mycobacterium tuberculosis. Here we demonstrate that rv1991c, one of the mazF homologue genes in M. tuberculosis, forms a TA system with its upstream open reading frame termed as rv1991a. It was found that Rv1991c is a toxin, leading to cell growth arrest through its endoribonuclease activity, while Rv1991a is an antitoxin against Rv1991c. Rv1991a inhibits the endoribonuclease activity of Rv1991c by interacting with Rv1991c to form the Rv1991a-Rv1991c complex. Both Rv1991a-Rv1991c complex and Rv1991a alone can bind to the promoter of rv1991a-rv1991c operon. Rv1991a binds to the promoter through a DNA-binding domain in its N-terminal region. Site-directed mutations of the highly conserved amino acid residues in the DNA-binding domain (S25A and R26A) disrupted the DNA-binding ability of Rv1991a. These results indicate that the rv1991a-rv1991c operon on M. tuberculosis genomic DNA is a typical TA system.