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Peer-reviewedCC BY 4.0The EMBO Journal

A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa

  • Tietao Wang1
  • Wenbo Yan1
  • Chenchen Wang2
  • Longgang Sang2
  • Yingxin Yang1
  • Jingru Zhao1
  • Chao Li1
  • Lijun Liu1,3
  • Yani Zhang1
  • Shuai Le4
  • Haihua Liang2
4 affiliations
  1. 1Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, China
  2. 2Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China
  3. 3School of Basic Medical Science, Xi’an Medical University, Xi’an, China
  4. 4Department of Microbiology, Army Medical University, Chongqing, China
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Abstract

To fully harness phage therapy against escalating antimicrobial resistance, it is imperative to elucidate the fundamental mechanisms by which viruses systematically dismantle host physiology. In this study, we identify Ped1, a protein from Pseudomonas aeruginosa phage PaoP5, which suppresses bacterial growth through two mechanisms: degradation of genomic DNA and direct inhibition of the replication machinery. Our 2.3-Å crystal structure and biochemical profiling reveal that Ped1 adopts a previously uncharacterized α/β-nuclease architecture, enabling the efficient cleavage of both double-stranded and single-stranded DNA. Furthermore, we demonstrate that Ped1 physically interacts with the host replicative helicase, DnaB, to suppress its activity during DNA replication. Reciprocally, DnaB binds Ped1 to neutralize its nuclease function, acting as an internal immunity partner. Evolutionary analysis indicates that Ped1 is a lineage-specific toxin strictly conserved among Pseudomonas phages. Collectively, this work identifies a novel, dual-function phage effector that coordinately disrupts genomic integrity and replication fidelity, thus advancing our understanding of the phage–host molecular arms race, and describing a promising scaffold for the development of next-generation antimicrobials against multidrug-resistant P. aeruginosa.

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Cite

BibTeXRIS
BibTeX
@article{wang2026dualaction,
  title = {{A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa}},
  author = {Tietao Wang and Wenbo Yan and Chenchen Wang and Longgang Sang and Yingxin Yang and Jingru Zhao and Chao Li and Lijun Liu and Yani Zhang and Shuai Le and Haihua Liang},
  journal = {The EMBO Journal},
  year = {2026},
  month = oct,
  doi = {10.1038/s44318-026-00924-8},
  url = {https://doi.org/10.1038/s44318-026-00924-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A dual-action bacteriophage protein Ped1 degrades DNA and blocks replication in Pseudomonas aeruginosa
AU  - Tietao Wang
AU  - Wenbo Yan
AU  - Chenchen Wang
AU  - Longgang Sang
AU  - Yingxin Yang
AU  - Jingru Zhao
AU  - Chao Li
AU  - Lijun Liu
AU  - Yani Zhang
AU  - Shuai Le
AU  - Haihua Liang
PY  - 2026
DA  - 2026/10/02
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00924-8
UR  - https://doi.org/10.1038/s44318-026-00924-8
AB  - To fully harness phage therapy against escalating antimicrobial resistance, it is imperative to elucidate the fundamental mechanisms by which viruses systematically dismantle host physiology. In this study, we identify Ped1, a protein from Pseudomonas aeruginosa phage PaoP5, which suppresses bacterial growth through two mechanisms: degradation of genomic DNA and direct inhibition of the replication machinery. Our 2.3-Å crystal structure and biochemical profiling reveal that Ped1 adopts a previously uncharacterized α/β-nuclease architecture, enabling the efficient cleavage of both double-stranded and single-stranded DNA. Furthermore, we demonstrate that Ped1 physically interacts with the host replicative helicase, DnaB, to suppress its activity during DNA replication. Reciprocally, DnaB binds Ped1 to neutralize its nuclease function, acting as an internal immunity partner. Evolutionary analysis indicates that Ped1 is a lineage-specific toxin strictly conserved among Pseudomonas phages. Collectively, this work identifies a novel, dual-function phage effector that coordinately disrupts genomic integrity and replication fidelity, thus advancing our understanding of the phage–host molecular arms race, and describing a promising scaffold for the development of next-generation antimicrobials against multidrug-resistant P. aeruginosa.
SN  - 0261-4189
SN  - 1460-2075
ER  -