Base-modified nucleotides mediate immune signaling in bacteria

• 成果类型: Article
• 署名作者: Zeng, Zhifeng; Hu, Zeyu; Zhao, Ruiliang; Rao, Jikai; Mestre, Mario Rodriguez; Liu, Yanqiu; Liu, Shunhang; Feng, Hao; Chen, Yu; He, Huan; Chen, Nuo; Zheng, Jinshui; Peng, Donghai; Luo, Min; She, Qunxin; Pinilla-Redondo, Rafael; Han, Wenyuan
• 署名单位: Huazhong Agricultural University; Hubei Hongshan Laboratory; Huazhong Agricultural University; University of Copenhagen; National University of Singapore; Huazhong Agricultural University; Huazhong Agricultural University; Shandong University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10113
• DOI: 10.1126/science.ads6055
• 发表日期: 2025-04-25
• 关键词: adenosine-deaminase; alignment; bacteriophage-t5; identification; DEFENSE; sensitivity; systems; cloning; kinase

摘要

Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. Whereas cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other messengers remains largely unexplored. In this study, we reveal a bacterial antiphage system that mediates immune signaling through nucleobase modification. Immunity is triggered by phage nucleotide kinases, which, combined with the system-encoded adenosine deaminase, produce deoxyinosine triphosphates (dITPs) as immune messengers. The dITP signal activates a downstream effector to mediate depletion of cellular nicotinamide adenine dinucleotide (oxidized form), resulting in population-level defense through the death of infected cells. To counteract immune signaling, phages deploy specialized enzymes that deplete cellular deoxyadenosine monophosphate, the precursor of dITP messengers. Our findings uncover a nucleobase modification-based antiphage signaling pathway, establishing noncanonical nucleotides as a new type of immune messengers in bacteria.