Page 20 - 《中国药科大学学报》2025年第4期

学报
416 Journal of China Pharmaceutical University 2025, 56(4): 416 − 423

细菌核酸感应系统的分子多样性与进化机制：

聚焦 CBASS 天然免疫系统

边雯婧，李 媚，肖易倍 *

（中国药科大学药理系, 南京 211198）

摘 要 细菌 CBASS 系统（cyclic-oligonucleotide-based anti-phage signaling system）是由环状核苷酸介导的新型先天免疫
防御机制。该系统通过 cGAS/DncV 样环核苷酸转移酶（cGAS/DncV-like nucleotidyltransferases，CD-NTase）识别外源核
酸，催化生成 cyclic GMP-AMP (cGAMP) 等第二信使分子，进而激活核酸酶等效应蛋白，最终触发“细胞自杀”以抵御噬菌体
感染。CBASS 的分子机制与进化特征不仅揭示了细菌免疫防御的多样性，也为理解原核-真核免疫通路的保守性提供了重要
线索。研究发现，细菌 CBASS 系统与真核生物的 cGAS-STING (cyclic GMP-AMP synthase−stimulator of interferon genes) 通
路在多个层面高度同源，包括 CD-NTase/cGAS 的催化结构域及环状核苷酸信号传导机制。这一发现揭示了真核先天免疫可
能起源于原核生物水平基因转移的假说，并表明防御策略从细菌的“群体裂解”进化至高等生物的“个体炎症激活”。本文系
统综述了 CBASS 系统的功能架构与作用机制，并深入探讨其与真核 cGAS-STING 通路的进化关联，为理解先天免疫系统的
起源与演化以及生物技术研发提供了新的视角。
关键词 CBASS 系统；cGAS-STING 通路；环状核苷酸；免疫进化
中图分类号 Q939.91 文献标志码 A 文章编号 1000−5048(2025)04−0416−08
doi：10.11665/j.issn.1000−5048.2025061603

引用本文 边雯婧，李媚，肖易倍. 细菌核酸感应系统的分子多样性与进化机制：聚焦 CBASS 天然免疫系统 [J]. 中国药科大学学报，2025，
56（4）：416 − 423.

Cite this article as: BIAN Wenjing, LI Mei, XIAO Yibei. Molecular diversity and evolutionary mechanisms of bacterial nucleic acid sensing
systems: a focus on the CBASS innate immune system[J]. J China Pharm Univ, 2025, 56(4): 416 − 423.

Molecular diversity and evolutionary mechanisms of bacterial nucleic acid
sensing systems: a focus on the CBASS innate immune system

BIAN Wenjing, LI Mei, XIAO Yibei *
Department of Pharmacology, China Pharmaceutical University, Nanjing 211198, China

Abstract The bacterial CBASS(cyclic-oligonucleotide-based anti-phage signaling system) represents a novel
innate immune defense mechanism mediated by cyclic nucleotides.The system employs cGAS/DncV-like
nucleotidyltransferases (CD-NTases) to recognize exogenous nucleic acids, catalyzing the production of second
messenger molecules such as cyclic GMP-AMP (cGAMP) to activate effector proteins (e.g., nucleases), thereby
triggering "cell suicide" to combat phage infection. The molecular mechanisms and evolutionary features of
CBASS not only uncover the diversity of bacterial immune defenses but also provide critical insights into the
conservation of prokaryotic-eukaryotic immune pathways. Notably, the bacterial CBASS system exhibits
profound homology with the eukaryotic cGAS-STING (Cyclic GMP-AMP Synthase—Stimulator of Interferon
Genes) pathway across multiple dimensions, including the catalytic domains of CD-NTase/cGAS and cyclic
nucleotide signaling mechanisms. This finding supports the hypothesis that eukaryotic innate immunity may have
originated from prokaryotic horizontal gene transfer and highlights an evolutionary shift in defense strategies

收稿日期 2025-06-16 * 通信作者 Tel：13120739565 E-mail：yibei.xiao@cpu.edu.cn