Moll Isabella, Engelberg-Kulka Hanna
Department of Microbiology, Immunobiology and Genetics, Center for Molecular Biology, University of Vienna, Max Perutz Labs, Vienna Biocenter (VBC), Vienna, Austria.
Departmen of Microbiology and Molecular Genetics, IMRIC, The Hebrew University Hadassah Medical School, Ein Karem Jerusalem, Israel.
Arch Mol Biol Genet. 2022;1(1):8-11. doi: 10.33696/genetics.1.002.
Bacterial communication via quorum sensing (QS) molecules, as well as toxin-antitoxin (TA) gene modules located on bacterial chromosomes are well-studied mechanisms. is a stress-induced TA system mediating cell death requiring a QS extracellular death factor (EDF), the pentapeptide NNWNN. MazF is an endoribonuclease specific for ACA sites. During adverse conditions, the activated MazF generates a stress induced translation machinery, composed of MazF-processed mRNAs and selective ribosomes that specifically translate these processed mRNAs. Moreover, we identified the molecular mechanism underlying the formation of EDF from the mRNA that involves distinct steps comprising the activity of MazF, the trans-translation system as well as the protease ClpPX. Bacterial trans-translation is generally known as a quality control process that rescues stalled translation complexes at the 3'-terminus of non-stop mRNAs. Our results indicate that trans-translation has a similar role in EDF generation from mRNA. However, our data reveal that the trans-translation system may also provide a regulatory mechanism to attenuate EDF generation in the single cells. Thereby, the required threshold of EDF molecules is only achieved by the entire bacterial population, as expected for a genuine QS process.
通过群体感应(QS)分子进行的细菌通讯以及位于细菌染色体上的毒素 - 抗毒素(TA)基因模块是经过充分研究的机制。是一种应激诱导的TA系统,介导细胞死亡,需要一种QS细胞外死亡因子(EDF),即五肽NNWNN。MazF是一种对ACA位点具有特异性的内切核糖核酸酶。在不利条件下,活化的MazF产生一种应激诱导的翻译机制,该机制由MazF加工的mRNA和特异性翻译这些加工后mRNA的选择性核糖体组成。此外,我们确定了从mRNA形成EDF的分子机制,该机制涉及包括MazF活性、反式翻译系统以及蛋白酶ClpPX在内的不同步骤。细菌反式翻译通常被认为是一种质量控制过程,可拯救非终止mRNA 3'末端停滞的翻译复合物。我们的结果表明,反式翻译在从mRNA产生EDF过程中具有类似作用。然而,我们的数据表明,反式翻译系统也可能提供一种调节机制,以减弱单细胞中EDF的产生。因此,正如真正的QS过程所预期的那样,只有整个细菌群体才能达到所需的EDF分子阈值。