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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

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

  • 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。

     

    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 from bacterial "population lysis" to "individual inflammatory activation" in higher organisms.This review systematically synthesizes the functional architecture and mechanisms of the CBASS system, with a deep exploration of its evolutionary connections to the eukaryotic cGAS-STING pathway. The insights gained herein offer fresh perspectives for understanding the origin and evolution of the innate immune system, and for driving advancements in biotechnological research and development.

     

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