Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Departments of Medicine and Genetics, Stanford University, Stanford, CA, USA.
Nat Microbiol. 2018 Jan;3(1):90-98. doi: 10.1038/s41564-017-0051-0. Epub 2017 Oct 30.
The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction-modification and CRISPR-Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction-modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction-modification systems. Our results suggest that DISARM is a new type of multi-gene restriction-modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.
噬菌体对细菌和古菌的捕食所施加的进化压力，导致了有效的抗噬菌体防御机制的发展，包括限制修饰和 CRISPR-Cas 系统。在这里，我们报告了一种新的防御系统，称为 DISARM（与限制修饰相关的防御岛系统），它广泛存在于细菌和古菌中。DISARM 由五个基因组成，包括一个 DNA 甲基化酶和另外四个被注释为解旋酶结构域、磷脂酶 D（PLD）结构域、DUF1998 结构域和一个未知功能基因。将 Bacillus paralicheniformis 9945a 的 DISARM 系统工程改造到 Bacillus subtilis 中，使工程细菌能够抵御来自所有三大类长尾双链 DNA 噬菌体的噬菌体。通过一系列基因缺失，我们表明五个基因中的四个对于 DISARM 介导的防御是必需的，而第五个（PLD）对于防御某些噬菌体是冗余的。我们进一步表明，DISARM 限制了进入的噬菌体 DNA，并且 B. paralicheniformis DISARM 甲基化酶将宿主 CCWGG 基序修饰为自我 DNA 的标记，类似于限制修饰系统。我们的结果表明，DISARM 是一种新型的多基因限制修饰模块，扩展了已知可用于原核生物抵御其病毒的防御系统的武器库。
