MazF 毒素导致金黄色葡萄球菌转录组、翻译组和蛋白质组发生改变，从而导致细菌休眠。
MazF toxin causes alterations in Staphylococcus aureus transcriptome, translatome and proteome that underlie bacterial dormancy.
机构信息
Department of Physics and Astronomy, The University of Manchester, Manchester M13 9PL, UK.
Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland.
出版信息
Nucleic Acids Res. 2021 Feb 26;49(4):2085-2101. doi: 10.1093/nar/gkaa1292.
Antibiotic resistance is a serious problem which may be caused by bacterial dormancy. It has been suggested that bacterial toxin-antitoxin systems induce dormancy. We analyzed the genome-wide role of Staphylococcus aureus endoribonuclease toxin MazF using RNA-Seq, Ribo-Seq and quantitative proteomics. We characterized changes in transcriptome, translatome and proteome caused by MazF, and proposed that MazF decreases translation directly by cleaving mRNAs, and indirectly, by decreasing translation factors and by promoting ribosome hibernation. Important pathways affected during the early stage of MazF induction were identified: MazF increases cell wall thickness and decreases cell division; MazF activates SsrA-system which rescues stalled ribosomes, appearing as a result of MazF mRNA cleavage. These pathways may be promising targets for new antibacterial drugs that prevent bacteria dormancy. Finally, we described the overall impact of MazF on S. aureus cell physiology, and propose one of the mechanisms by which MazF might regulate cellular changes leading to dormancy.
抗生素耐药性是一个严重的问题，可能是由细菌休眠引起的。有人提出，细菌毒素-抗毒素系统诱导休眠。我们使用 RNA-Seq、Ribo-Seq 和定量蛋白质组学分析了金黄色葡萄球菌内切核糖核酸酶毒素 MazF 的全基因组作用。我们描述了 MazF 引起的转录组、翻译组和蛋白质组的变化，并提出 MazF 通过切割 mRNA 直接降低翻译，通过降低翻译因子和促进核糖体休眠间接降低翻译。在 MazF 诱导的早期阶段确定了受影响的重要途径：MazF 增加细胞壁厚度并减少细胞分裂；MazF 激活 SsrA 系统，挽救停滞的核糖体，这是 MazF mRNA 切割的结果。这些途径可能是预防细菌休眠的新型抗菌药物的有前途的靶点。最后，我们描述了 MazF 对金黄色葡萄球菌细胞生理学的整体影响，并提出了 MazF 可能调节导致休眠的细胞变化的机制之一。
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