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Phage homing endonuclease amplifies anti-defense genes to evade bacterial immunity

Chihara, Kotaro ; Azam, Aa Haeruman ; Egorov, Artyom A LU orcid ; Terenin, Ilya LU orcid ; Hashino, Masanori ; Watashi, Koichi ; Horiba, Kazuhiro ; Hauryliuk, Vasili LU orcid and Kiga, Kotaro (2026) In Nature Communications 17. p.1-16
Abstract

Bacteriophages must overcome diverse bacterial immune systems, yet the molecular principles enabling such escape remain poorly understood. Here, we show that the phage homing endonuclease SegB facilitates immune evasion by promoting the segmental amplification of anti-defense loci. The antiphage defense Septu inhibits phage T6 replication by cleaving the variable loop of tRNATyr. We show that SegB enables immune evasion by amplifying a genomic segment that contains the full-length tRNATyr gene. This repeat expansion increases tRNATyr expression, allowing the phage to overcome Septu immunity. SegB also mediates in trans amplification of distinct anti-defense genes that counteract OLD and toxin-antitoxin... (More)

Bacteriophages must overcome diverse bacterial immune systems, yet the molecular principles enabling such escape remain poorly understood. Here, we show that the phage homing endonuclease SegB facilitates immune evasion by promoting the segmental amplification of anti-defense loci. The antiphage defense Septu inhibits phage T6 replication by cleaving the variable loop of tRNATyr. We show that SegB enables immune evasion by amplifying a genomic segment that contains the full-length tRNATyr gene. This repeat expansion increases tRNATyr expression, allowing the phage to overcome Septu immunity. SegB also mediates in trans amplification of distinct anti-defense genes that counteract OLD and toxin-antitoxin ToxIN defense systems. Collectively, our findings demonstrate that SegB-mediated segmental amplification represents a versatile mechanism by which phages rapidly adapt to and circumvent diverse bacterial antiphage defenses.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Endonucleases/metabolism, Immune Evasion/genetics, Bacteriophages/enzymology, Viral Proteins/metabolism, Bacteria/virology, Escherichia coli/virology
in
Nature Communications
volume
17
article number
3468
pages
1 - 16
publisher
Nature Publishing Group
external identifiers
  • pmid:42009657
ISSN
2041-1723
DOI
10.1038/s41467-026-71036-4
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
578fb865-5c30-47b2-898c-dd1478cd2121
date added to LUP
2026-04-21 16:56:07
date last changed
2026-04-22 07:30:00
@article{578fb865-5c30-47b2-898c-dd1478cd2121,
  abstract     = {{<p>Bacteriophages must overcome diverse bacterial immune systems, yet the molecular principles enabling such escape remain poorly understood. Here, we show that the phage homing endonuclease SegB facilitates immune evasion by promoting the segmental amplification of anti-defense loci. The antiphage defense Septu inhibits phage T6 replication by cleaving the variable loop of tRNA<sup>Tyr</sup>. We show that SegB enables immune evasion by amplifying a genomic segment that contains the full-length tRNA<sup>Tyr</sup> gene. This repeat expansion increases tRNA<sup>Tyr </sup>expression, allowing the phage to overcome Septu immunity. SegB also mediates in trans amplification of distinct anti-defense genes that counteract OLD and toxin-antitoxin ToxIN defense systems. Collectively, our findings demonstrate that SegB-mediated segmental amplification represents a versatile mechanism by which phages rapidly adapt to and circumvent diverse bacterial antiphage defenses.</p>}},
  author       = {{Chihara, Kotaro and Azam, Aa Haeruman and Egorov, Artyom A and Terenin, Ilya and Hashino, Masanori and Watashi, Koichi and Horiba, Kazuhiro and Hauryliuk, Vasili and Kiga, Kotaro}},
  issn         = {{2041-1723}},
  keywords     = {{Endonucleases/metabolism; Immune Evasion/genetics; Bacteriophages/enzymology; Viral Proteins/metabolism; Bacteria/virology; Escherichia coli/virology}},
  language     = {{eng}},
  month        = {{04}},
  pages        = {{1--16}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Phage homing endonuclease amplifies anti-defense genes to evade bacterial immunity}},
  url          = {{http://dx.doi.org/10.1038/s41467-026-71036-4}},
  doi          = {{10.1038/s41467-026-71036-4}},
  volume       = {{17}},
  year         = {{2026}},
}