Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA.
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Cell. 2023 May 25;186(11):2410-2424.e18. doi: 10.1016/j.cell.2023.04.015. Epub 2023 May 8.
Bacteria use a wide range of immune pathways to counter phage infection. A subset of these genes shares homology with components of eukaryotic immune systems, suggesting that eukaryotes horizontally acquired certain innate immune genes from bacteria. Here, we show that proteins containing a NACHT module, the central feature of the animal nucleotide-binding domain and leucine-rich repeat containing gene family (NLRs), are found in bacteria and defend against phages. NACHT proteins are widespread in bacteria, provide immunity against both DNA and RNA phages, and display the characteristic C-terminal sensor, central NACHT, and N-terminal effector modules. Some bacterial NACHT proteins have domain architectures similar to the human NLRs that are critical components of inflammasomes. Human disease-associated NLR mutations that cause stimulus-independent activation of the inflammasome also activate bacterial NACHT proteins, supporting a shared signaling mechanism. This work establishes that NACHT module-containing proteins are ancient mediators of innate immunity across the tree of life.
细菌利用广泛的免疫途径来对抗噬菌体感染。这些基因的一部分与真核生物免疫系统的成分具有同源性，这表明真核生物从细菌中水平获得了某些先天免疫基因。在这里，我们表明，含有 NACHT 模块的蛋白质（动物核苷酸结合域和富含亮氨酸重复基因家族（NLRs）的核心特征）存在于细菌中并可抵抗噬菌体。NACHT 蛋白在细菌中广泛存在，可提供针对 DNA 和 RNA 噬菌体的免疫，并且具有特征性的 C 末端传感器，中央 NACHT 和 N 末端效应子模块。一些细菌 NACHT 蛋白具有与人类 NLR 相似的结构域，后者是炎症小体的关键组成部分。导致炎症小体刺激非依赖性激活的人类疾病相关 NLR 突变也可激活细菌 NACHT 蛋白，支持共享的信号转导机制。这项工作确立了含有 NACHT 模块的蛋白质是生命之树中古老的先天免疫介质。
