Skip to content
Snippets Groups Projects
Select Git revision
  • main default protected
  • dev protected
  • tclabby-main-patch-92350
  • tclabby-main-patch-26246
  • operon-struct-type
  • operon-struct-type-article
  • remove-duplicate-structure-Lamassu-Fam_PDDEXK
  • operon-struct-type-article-update
  • system-distribution-plot
  • update-article-auto-sections
  • genome-context-system
  • select-columns
  • mao
  • ftesson_abip2
  • ftesson_abia
  • ftesson_abij
  • ftesson_abiz
  • ftesson_abie
  • ftesson_abir
  • ftesson_abii
20 results
Blame History Permalink
disarm.md 4.38 KiB 
title: DISARM

Description

DISARM (Defense Island System Associated with Restriction-Modification) is a defense system widespread in prokaryotes, encoded by a 5-gene cassette. DISARM provides broad protection against double-stranded DNA phages, including siphophages, myophages, and podophages (1,3).

 It was reported to restrict incoming phage DNA and methylate the bacterial host DNA, which could be responsible for self from non-self discrimination (1). This suggests a Restriction-Modification-like (RM-like) mechanism, yet some pieces of experimental evidence hint that DISARM actually acts through a novel and uncharacterized molecular mechanism (1,2).

Molecular mechanism

DISARM allows phage adsorption but prevents phage replication. DISARM is thought to cause intracellular phage DNA decay (1), but the molecular of this potential DNA degradation remains unknown.

The drmMII gene of DISARM system from Bacillus paralicheniformis was shown to methylate bacterial DNA at CCWGG motifs when expressed in Bacillus subtilis, and in the absence of drmMII, this DISARM system appears toxic to the cells (1). These observations are consistent with an RM-like mechanism, where nucleic acid degradation targets specific DNA motifs, that are methylated in the bacterial chromosome to prevent auto-immunity. 

Yet this system was also shown to protect against phages whose genomes are exempt of CCWGG motifs (1). Moreover, a recent study reports that the absence of methylases (DrmMI or DrmMII) of the DISARM system from a Serratia sp. does not result in autoimmunity (3). Both these results suggest additional phage DNA recognition mechanisms. 

Hints of these additional mechanisms can be found in recent structural studies, which show that DrmA and DrmB form a complex that can bind single-stranded DNA (2). Moreover, the DrmAB complex seems to exhibit strong ATPase activity in presence of unmethylated DNA, and  reduced ATPase activity in the presence of a methylated DNA substrate (2). Finally, binding of unmethylated single-stranded DNA appears to mediate major conformational change of the complex, which was hypothesized to be responsible for downstream DISARM activation (2).

Example of genomic structure

DISARM is encoded by three core genes: drmA (encoding for a protein containing a putative helicase domain), drmB (encoding for a protein containing a putative helicase-associated domain), and drmC (encoding for a protein containing a phospholipase D/nuclease domain) (1)

These three core genes are accompanied by a methyltransferase, which can be either an adenine methylase (drmMI) for class 1 DISARM systems or a cytosine methylase (drmMII) for DISARM class 2. Both classes also encode an additional gene (drmD for class 1, and drmE for class 2). 

Here is some example found in the RefSeq database:

disarm

DISARM_1 subsystem in the genome of Pseudomonas aeruginosa (GCF_009676885.1) is composed of 6 proteins: drmD (WP_023093122.1), drmMI (WP_023115027.1), drmD (WP_023093126.1), drmA (WP_033993408.1), drmB (WP_023093129.1)and, drmC (WP_031637507.1).

disarm

DISARM_2 subsystem in the genome of Bacillus paralicheniformis (GCF_009497935.1) is composed of 5 proteins: drmMII (WP_020450482.1), drmC (WP_020450481.1), drmB (WP_025810358.1), drmA (WP_020450479.1)and, drmE (WP_020450478.1).

Distribution of the system among prokaryotes

The DISARM system is present in a total of 214 different species.

Among the 22k complete genomes of RefSeq, this system is present in 341 genomes (1.5 %).

disarm

Proportion of genome encoding the DISARM system for the 14 phyla with more than 50 genomes in the RefSeq database. Pie chart of the repartition of all the subsystems found in the RefSeq database.

Experimental validation

DISARM systems were experimentally validated using:

A system from Bacillus paralicheniformis in Bacillus subtilis has an anti-phage effect against SPO1, phi3T, SpBeta, SPR, phi105, rho14, SPP1, phi29 , Nf (Doron et al., 2018; Ofir et al., 2017)

A system from Serratia sp. SCBI in Escherichia coli has an anti-phage effect against T1, Nami, T7, M13 (Aparicio-Maldonado et al., 2021)

Relevant abstracts

::article-doi-list

items: - 10.1038/s41467-022-30673-1 - 10.1038/s41564-017-0051-0

::