Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
Bioprotection Aotearoa, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
Nucleic Acids Res. 2022 Apr 8;50(6):3348-3361. doi: 10.1093/nar/gkac147.
Epigenetic DNA methylation plays an important role in bacteria by influencing gene expression and allowing discrimination between self-DNA and intruders such as phages and plasmids. Restriction-modification (RM) systems use a methyltransferase (MTase) to modify a specific sequence motif, thus protecting host DNA from cleavage by a cognate restriction endonuclease (REase) while leaving invading DNA vulnerable. Other REases occur solitarily and cleave methylated DNA. REases and RM systems are frequently mobile, influencing horizontal gene transfer by altering the compatibility of the host for foreign DNA uptake. However, whether mobile defence systems affect pre-existing host defences remains obscure. Here, we reveal an epigenetic conflict between an RM system (PcaRCI) and a methylation-dependent REase (PcaRCII) in the plant pathogen Pectobacterium carotovorum RC5297. The PcaRCI RM system provides potent protection against unmethylated plasmids and phages, but its methylation motif is targeted by the methylation-dependent PcaRCII. This potentially lethal co-existence is enabled through epigenetic silencing of the PcaRCII-encoding gene via promoter methylation by the PcaRCI MTase. Comparative genome analyses suggest that the PcaRCII-encoding gene was already present and was silenced upon establishment of the PcaRCI system. These findings provide a striking example for selfishness of RM systems and intracellular competition between different defences.
表观遗传 DNA 甲基化在细菌中起着重要作用，通过影响基因表达并允许区分自身 DNA 和噬菌体和质粒等入侵者。限制修饰（RM）系统使用甲基转移酶（MTase）修饰特定的序列基序，从而保护宿主 DNA 免受同源限制内切酶（REase）的切割，同时使入侵 DNA 易受攻击。其他 REase 则单独存在并切割甲基化 DNA。REase 和 RM 系统经常发生移动，通过改变宿主对外国 DNA 摄取的兼容性来影响水平基因转移。然而，移动防御系统是否会影响宿主预先存在的防御机制尚不清楚。在这里，我们揭示了植物病原菌果胶杆菌 RC5297 中 RM 系统（PcaRCI）和依赖于甲基化的 REase（PcaRCII）之间的表观遗传冲突。PcaRCI RM 系统为未甲基化的质粒和噬菌体提供了强大的保护，但它的甲基化基序是依赖甲基化的 PcaRCII 的靶标。这种潜在的致命共存是通过 PcaRCI MTase 对 PcaRCII 编码基因的启动子甲基化来实现的，从而导致 PcaRCII 编码基因的表观遗传沉默。比较基因组分析表明，PcaRCII 编码基因已经存在，并在 PcaRCI 系统建立时被沉默。这些发现为 RM 系统的自私性和不同防御机制之间的细胞内竞争提供了一个惊人的例子。
