Structural basis for broad anti-phage immunity by DISARM

Bravo, Jack P.K.; Maldonado, Cristian A; Nóbrega, Franklin L.; Brouns, Stan J. J.; Taylor, David W.

doi:10.1101/2021.12.26.474123

Cited by 3 publications

(2 citation statements)

References 64 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5B). As the viral MTase contributes to escape from the bacterial restriction-modification systems by methylating their DNA [33], diversifying the pattern of MTase by frequent homologous recombination suggests a strain-level adaptation strategy of viruses against the internal immune mechanisms of host bacteria.…”

Section: Comparative Genomics Reveals the Profiles Of Methyltransfera...mentioning

confidence: 99%

Large-scale single-virus genomics uncovers hidden diversity of river water viruses and diversified gene profiles

Nishikawa,

Wagatsuma,

Tsukada

et al. 2024

Preprint

View full text Add to dashboard Cite

Environmental viruses (primarily bacteriophages) are widely recognized as playing an important role in ecosystem homeostasis through the infection of host cells. However, the majority of environmental viruses are still unknown as their mosaic structure and frequent mutations in their sequences hinder genome construction in current metagenomics. To enable the large-scale acquisition of environmental viral genomes, we developed a new single-viral genome sequencing platform with microfluidic-generated gel beads. Amplification of individual DNA viral genomes in mass-produced gel beads allows high-throughput genome sequencing compared to conventional single-virus genomics. The sequencing analysis of river water samples yielded 1431 diverse viral single-amplified genomes, while viral metagenomics recovered 100 viral metagenome-assembled genomes at the comparable sequence depth. The 99.5% of viral single-amplified genomes were determined novel at the species level, most of which could not be recovered by a metagenomic assembly. The large-scale acquisition of diverse viral genomes identified protein clusters commonly detected in different viral strains, allowing the gene transfer to be tracked. Moreover, comparative genomics within the same viral species revealed that the profiles of various methyltransferase subtypes were diverse, suggesting an enhanced escape from host bacterial internal defense mechanisms. Our use of gel bead-based single-virus genomics will contribute to exploring the nature of viruses by accelerating the accumulation of draft genomes of environmental DNA viruses.

show abstract

Section: Comparative Genomics Reveals the Profiles Of Methyltransfera...mentioning

confidence: 99%

Large-scale single-virus genomics uncovers hidden diversity of river water viruses and diversified gene profiles

Nishikawa,

Wagatsuma,

Tsukada

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…However, most of the defence systems were discovered recently [2][3][4][5][6][7][8][9][10] and their molecular mechanisms are not well understood beyond their anti-phage functions. Research on some of these novel defence systems, such as BREX 5,11,12 , DISARM 4,13,14 , CBASS 15,16 , Thoeris 17,18 , Pycsar 19 , PARIS 8 , Gabija 3,20,21 , Retrons 22 , RADAR 6,23,24 , DSR 25 , Avast 6,26 , Gasdermins 27 , dCTP deaminase, dGTPase 28,29 , and pVips 30 , has made significant progress in elucidating their molecular activities. Further research is needed to fully characterise the dozens of defence systems that remain to be explored.…”

mentioning

confidence: 99%

Kiwa rescues RecBCD for anti-phage activity

Todeschini

Naji

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Bacteria have evolved numerous defence systems to combat phage infection, but our understanding of the underlying mechanisms is limited beyond their antiviral function. Here, we provide mechanistic insights into the Kiwa defence system, which is composed of two proteins, the transmembrane protein KwaA and the DUF4868 domain-containing protein KwaB. Using Kiwa from Escherichia coli ECOR8 and ECOR12, we found that KwaA detects phage infection by sensing inhibition of the host RNA polymerase. Consequently, the inhibitory effect of KwaA on the effector protein KwaB is relieved, which results in decreased phage DNA replication efficiency through a RecBCD-dependent pathway. Notably, Kiwa restores RecBCD activity even against phages that encode anti-RecBCD proteins. Our findings also reveal that KwaB has antiphage activity in the absence of both KwaA and phage trigger, but the conserved two-protein Kiwa operon implies that strict regulation of KwaB activity by KwaA is necessary to prevent potential auto-immunity.

show abstract

Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition

Aparicio-Maldonado

Ofir

Salini

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Bacteriophages impose a strong evolutionary pressure on microbes for the development of mechanisms of survival. Multiple new mechanisms of innate defense have been described recently, with the molecular mechanism of most of them remaining uncharacterized. Here, we show that a Class 1 DISARM (defense island system associated with restriction-modification) system from Serratia sp. provides broad protection from double-stranded DNA phages, and drives a population of single-stranded phages to extinction. We identify that protection is not abolished by deletion of individual DISARM genes and that the absence of methylase genes drmMI and drmMII does not result in autoimmunity. In addition to antiphage activity we also observe that DISARM limits conjugation, and this activity is linked to the number of methylase cognate sites in the plasmid. Overall, we show that Class 1 DISARM provides robust anti-phage and anti-plasmid protection mediated primarily by drmA and drmB, which provide resistance to invading nucleic acids using a mechanism enhanced by the recognition of unmethylated cognate sites of the two methylases drmMI and drmMII.

show abstract

Structural basis for broad anti-phage immunity by DISARM

Cited by 3 publications

References 64 publications

Large-scale single-virus genomics uncovers hidden diversity of river water viruses and diversified gene profiles

Large-scale single-virus genomics uncovers hidden diversity of river water viruses and diversified gene profiles

Kiwa rescues RecBCD for anti-phage activity

Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition

Contact Info

Product

Resources

About