Toxin-antitoxin vapBC locus participates in formation of the dormant state in Mycobacterium smegmatis
Toxin-antitoxin vapBC locus participates in formation of the dormant state in Mycobacterium smegmatis
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DOI：
10.1111/1574-6968.12380
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发表时间：
2014-03-01
影响因子：
2.1
通讯作者：
Goncharenko, Anna V.
中科院分区：
文献类型：
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作者：
Demidenok, Oksana I.;Kaprelyants, Arseny S.;Goncharenko, Anna V.
毒素-抗毒素（TA）基因座广泛分布于细菌质粒和染色体中。毒素影响细菌细胞的重要功能，如翻译、复制和细胞壁合成，而抗毒素是毒素抑制剂。参与细菌休眠状态的形成被认为是毒素的一个可能的功能。在这里，我们表明，在耻垢分枝杆菌的VapC毒素过表达的结果在形态上不同的卵圆形细胞的发展。卵圆形细胞是非复制的，并揭示了低水平的尿嘧啶掺入和呼吸，表明其休眠状态。为了验证VapBC在休眠形成中的作用，我们使用了在钾限制条件下获得的休眠、不可培养（NC）的耻垢分枝杆菌细胞模型。VapB抗毒素的过度表达防止过渡到休眠，大概是由于自由VapC蛋白的水平降低。事实上，VapB的这种作用被作为vapBC操纵子的一部分的同源VapC的共表达所中和。总之，这些研究结果揭示了参与vapBC产品在形成的休眠状态的耻垢分枝杆菌。
Toxin-antitoxin (TA) loci are widely spread in bacterial plasmids and chromosomes. Toxins affect important functions of bacterial cells such as translation, replication and cell-wall synthesis, whereas antitoxins are toxin inhibitors. Participation in formation of the dormant state in bacteria is suggested to be a possible function of toxins. Here we show that overexpression of VapC toxin in Mycobacterium smegmatis results in development of morphologically distinct ovoid cells. The ovoid cells were nonreplicating and revealed a low level of uracil incorporation and respiration that indicated their dormant status. To validate the role of VapBC in dormancy formation, we used a model of dormant, nonculturable' (NC) M.smegmatis cells obtained in potassium-limited conditions. Overexpression of VapB antitoxin prevented transition to dormancy, presumably due to a decreased level of the free VapC protein. Indeed, this effect of the VapB was neutralized by coexpression of the cognate VapC as a part of the vapBC operon. In summary, these findings reveal participation of vapBC products in formation of the dormant state in M.smegmatis.