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.

细菌利用多种免疫途径来对抗噬菌体感染。这些基因的一个子集与真核免疫系统的组成部分具有同源性，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，我们发现，在细菌中发现了含有 NACHT 模块的蛋白质，该模块是动物核苷酸结合结构域和富含亮氨酸重复序列的基因家族 (NLR) 的核心特征，并且可以防御噬菌体。 NACHT 蛋白广泛存在于细菌中，提供针对 DNA 和 RNA 噬菌体的免疫力，并显示出特征性的 C 端传感器、中央 NACHT 和 N 端效应器模块。一些细菌 NAHT 蛋白具有与人类 NLR 类似的结构域，而人类 NLR 是炎症小体的关键组成部分。人类疾病相关的 NLR 突变会导致炎症小体的非刺激依赖性激活，也会激活细菌 NACHT 蛋白，支持共同的信号传导机制。这项工作证实，含有 NAHT 模块的蛋白质是整个生命树先天免疫的古老介质。