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The early injected genomic region determines sensitivity to Type I restriction-modification defence against

Andrea Martinez-Cazorla1, Christian Martinez-Jimenez1, Patricia Elio-Lucas1

  • 1Department of Genetics and Microbiology, University of Murcia, Murcia 30100, Spain.

Nucleic Acids Research
|September 23, 2025
PubMed

Insights

Marinomonas mediterranea uses a Type I restriction-modification system (Mme2I) to block phages. Phages evade this bacterial defense by lacking the Mme2I motif in their initially injected DNA region, not just anywhere in the genome.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genomics

Background:

  • Bacteriophages employ various strategies to overcome bacterial defense mechanisms for successful infection.
  • Type I restriction-modification (RM) systems are key bacterial defenses that target and degrade foreign DNA lacking specific methylation patterns.
  • Understanding phage-host interactions is crucial for deciphering microbial community dynamics and developing phage-based therapies.

Purpose of the Study:

  • To investigate the role of the Type I RM system (Mme2I) in Marinomonas mediterranea MMB-2 against phage infection.
  • To determine the specific DNA sequence motif recognized by Mme2I and its significance in phage resistance.
  • To explore how the location of RM recognition sites influences phage escape strategies.

Main Methods:

  • Whole-genome sequencing of Marinomonas mediterranea MMB-2 and infecting phages.
  • DNA methylation analysis to identify methylated motifs.
  • Comparative genomics to analyze phage genome organization and motif presence.
  • Infection assays with wild-type and mutant phages to assess Mme2I efficacy.

Main Results:

  • Marinomonas mediterranea MMB-2 possesses a Type I RM system, Mme2I, that restricts infection by several Murciavirus phages.
  • A specific DNA motif, methylated in M. mediterranea MMB-2, was identified and found in the genomes of susceptible phages.
  • Phages lacking this motif in their leading DNA region, regardless of its presence elsewhere, successfully infected M. mediterranea MMB-2.
  • RM systems appear to influence the organization of the leading injected regions of phage genomes.

Conclusions:

  • The location of RM recognition motifs, particularly in the leading injected DNA, is critical for phage evasion of bacterial restriction systems.
  • Type I RM systems play a significant role in shaping the genomic architecture of phage leading regions, influencing the evolution of anti-defense mechanisms.

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