Peer-reviewedCC BY-NC-NDNature Communications
Mechanistic insights into activation of bacterial Retron-Eco8 immunity by phage protein SSB
7 affiliations
- 1Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China
- 2Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections, Department of Critical Medicine, School of Medicine, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China
- 3Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China. [email protected]
- 4Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China. [email protected]
- 5Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections, Department of Critical Medicine, School of Medicine, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China. [email protected]
- 6Department of Critical Care Medicine, Shenzhen People's Hospital, First Affiliated Hospital of Southern University of Science and Technology, Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China. [email protected]
- 7Shenzhen Key Laboratory of Cell Microenvironment, Key University Laboratory of Metabolism and Health of Guangdong, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, China. [email protected]
Abstract
The Retron-Eco8 system, comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and an OLD-family nuclease effector, protects bacteria from phage infection via abortive infection upon sensing a phage single-stranded DNA-binding protein (SSB). However, the molecular basis of this immunity remained unclear. Here, we report cryo-electron microscopy (cryo-EM) structures of Retron-Eco8 in inactive and activated states, revealing mechanisms of phage-triggered activation and effector function. Retron-Eco8 assembles into a tetrameric complex in which each protomer contains an RT, msrRNA–msdDNA duplex, and effector in an autoinhibited conformation. Upon phage infection, phage SSB binds msdDNA, relieving autoinhibition and activating the nuclease effector to degrade both phage and host DNA, triggering cell death to block phage propagation. Host SSB fails to activate the system, while DNA binding and oligomerization of phage SSB are essential for this activation, highlighting its specificity. These findings elucidate the molecular mechanism of Retron-Eco8-mediated immunity, facilitating retron-based biotechnological applications.
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BibTeX
@article{ji2026mechanistic,
title = {{Mechanistic insights into activation of bacterial Retron-Eco8 immunity by phage protein SSB}},
author = {Chao-Guang Ji and Zhuolin Li and Xin-Yang Wei and Y Li and Juntao Zhang and Xueyan Liu and Ning Jia},
journal = {Nature Communications},
year = {2026},
month = jun,
doi = {10.1038/s41467-026-74106-9},
url = {https://doi.org/10.1038/s41467-026-74106-9},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mechanistic insights into activation of bacterial Retron-Eco8 immunity by phage protein SSB
AU - Chao-Guang Ji
AU - Zhuolin Li
AU - Xin-Yang Wei
AU - Y Li
AU - Juntao Zhang
AU - Xueyan Liu
AU - Ning Jia
PY - 2026
DA - 2026/06/10
JO - Nature Communications
DO - 10.1038/s41467-026-74106-9
UR - https://doi.org/10.1038/s41467-026-74106-9
AB - The Retron-Eco8 system, comprising a reverse transcriptase (RT), a non-coding RNA (ncRNA), and an OLD-family nuclease effector, protects bacteria from phage infection via abortive infection upon sensing a phage single-stranded DNA-binding protein (SSB). However, the molecular basis of this immunity remained unclear. Here, we report cryo-electron microscopy (cryo-EM) structures of Retron-Eco8 in inactive and activated states, revealing mechanisms of phage-triggered activation and effector function. Retron-Eco8 assembles into a tetrameric complex in which each protomer contains an RT, msrRNA–msdDNA duplex, and effector in an autoinhibited conformation. Upon phage infection, phage SSB binds msdDNA, relieving autoinhibition and activating the nuclease effector to degrade both phage and host DNA, triggering cell death to block phage propagation. Host SSB fails to activate the system, while DNA binding and oligomerization of phage SSB are essential for this activation, highlighting its specificity. These findings elucidate the molecular mechanism of Retron-Eco8-mediated immunity, facilitating retron-based biotechnological applications.
SN - 2041-1723
ER -