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, WenyuanHan

Science 0, eads6055, https://www.science.org/doi/10.1126/science.ads6055

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.

原文链接：https://www.science.org/doi/10.1126/science.ads6055