DISARM is a widespread bacterial defence system with broad anti-phage activities

Abstract

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), that is widespread in bacteria and archaea. DISARM is comprised 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 3 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.

Phages actively challenge niche communities in the Antarctic soils

“…A total of 3758 genes for the DISARM system were identified. These included the Class I marker gene drmD (449 counts, 11.9% of DISARM genes), which encodes the SNF2-like helicase (23), as well as the Class II marker gene drmA (1020, 17.1% of DISARM genes), which encodes a protein with a putative helicase domain (23). Similarly, a total of 4598 genes representing all BREX types were identified in the metagenome.…”

“…These include adaptive immunity elements, such as the CRISPR-Cas systems, and innate immunity mechanisms, such as restriction-modification (RM) and toxin-antitoxin abortive infection (Abi) systems (18). Recent pangenomics studies have also identified novel defense systems that are widely distributed across bacterial taxa and are thought to play a role in anti-phage resistance (20–23). These include the bacteriophage exclusion (BREX) system, coded by a 4-8 gene cluster, that provides resistance to Siphoviridae and Myoviridae tailed phages by inhibition of phage DNA replication (21), and other less well characterized systems such as the Thoeris, Shedu and Gabija elements that increase bacterial host resistance to specific groups of phages (22).…”

Mycobacteriophages

“…These include the well-studied restriction-modification and CRISPR-Cas systems, but there are numerous examples of defense by abortive infection (abi) and a plethora of new defense systems have been identified (86, 87). Some mycobacterial strains – including M. tuberculosis – have CRISPR-Cas-like arrays, although their functionality in defense and spacer acquisition is unclear (88); mycobacterial restriction-modifications have also been described (89–92).…”

Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

“…In the replication step, bacteria have some well characterised counter attack strategies. Many of these defence strategies utilise DNA cutting, which can target the phage genome. Interestingly, some of the systems have been applied as advance tools in molecular biology.…”