碱基修饰的核苷酸介导细菌的免疫信号，这一成果由华中农业大学
该课题组研究人员揭示了一种细菌抗噬菌体系统，通过核碱基修饰介导免疫信号。免疫是由噬菌体核苷酸激酶触发的，它与系统编码的腺苷脱氨酶结合，产生脱氧肌苷5 '' -三磷酸（dITP）作为免疫信使。dITP信号激活下游效应物介导细胞NAD+耗竭，通过感染细胞的死亡导致群体水平的防御。为了对抗免疫信号，噬菌体使用专门的酶来消耗细胞中的dAMP，即dITP信使的前体。他们的发现揭示了一种基于核碱基修饰的抗噬菌体信号通路，建立了非典型核苷酸作为细菌中一种新型的免疫信使。
研究人员表示，从病原体感知到效应激活的信号传导是细胞免疫的基本原理。虽然环（寡核苷酸）已成为关键的信号分子，但其他信使的存在仍未得到充分探索。
附：英文原文
Title: Base-modified nucleotides mediate immune signaling in bacteria
Author: Zhifeng Zeng, Zeyu Hu, Ruiliang Zhao, Jikai Rao, Mario Rodríguez Mestre, Yanqiu Liu, Shunhang Liu, Hao Feng, Yu Chen, Huan He, Nuo Chen, Jinshui Zheng, Donghai Peng, Min Luo, Qunxin She, Rafael Pinilla-Redondo, Wenyuan Han
Issue&Volume: 2025-02-20
Abstract: Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. While cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of other messengers remains largely unexplored. Here, we reveal a bacterial anti-phage 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 5′-triphosphate (dITP) as immune messengers. The dITP signal activates downstream effector to mediate cellular NAD+ depletion, resulting in population-level defense through the death of infected cells. To counteract immune signaling, phages deploy specialized enzymes that deplete cellular dAMP, the precursor of dITP messengers. Our findings uncover a nucleobase modification-based anti-phage signaling pathway, establishing noncanonical nucleotides as a new type of immune messengers in bacteria.
DOI: ads6055
Source: https://www.science.org/doi/10.1126/science.ads6055