Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
de Botton Institute for Protein Profiling, The Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
Nat Commun. 2024 Nov 14;15(1):9860. doi: 10.1038/s41467-024-54214-0.
Antiviral STANDs (Avs) are bacterial anti-phage proteins evolutionarily related to immune pattern recognition receptors of the NLR family. Type 2 Avs proteins (Avs2) were suggested to recognize the phage large terminase subunit as a signature of phage infection. Here, we show that Avs2 from Klebsiella pneumoniae (KpAvs2) can recognize several different phage proteins as signature for infection. While KpAvs2 recognizes the large terminase subunit of Seuratvirus phages, we find that to protect against Dhillonvirus phages, KpAvs2 recognizes a different phage protein named KpAvs2-stimulating protein 1 (Ksap1). KpAvs2 directly binds Ksap1 to become activated, and phages mutated in Ksap1 escape KpAvs2 defense despite encoding an intact terminase. We further show that KpAvs2 protects against a third group of phages by recognizing another protein, Ksap2. Our results exemplify the evolutionary diversification of molecular pattern recognition in bacterial Avs2, and show that a single pattern recognition receptor evolved to recognize different phage-encoded proteins.
抗病毒 STAND（Avs）是与 NLR 家族的免疫模式识别受体在进化上相关的细菌抗噬菌体蛋白。有人提出，2 型 Avs 蛋白（Avs2）可以识别噬菌体大终止酶亚基作为噬菌体感染的特征。在这里，我们表明来自肺炎克雷伯氏菌的 Avs2（KpAvs2）可以识别几种不同的噬菌体蛋白作为感染的特征。虽然 KpAvs2 识别 Seuratvirus 噬菌体的大终止酶亚基，但我们发现为了抵御 Dhillonvirus 噬菌体，KpAvs2 识别一种名为 KpAvs2 刺激蛋白 1（Ksap1）的不同噬菌体蛋白。KpAvs2 直接结合 Ksap1 以被激活，并且尽管编码完整的终止酶，突变的噬菌体仍能逃避 KpAvs2 的防御。我们进一步表明，KpAvs2 通过识别另一种蛋白 Ksap2 来保护免受第三组噬菌体的侵害。我们的结果例证了细菌 Avs2 中分子模式识别的进化多样化，并表明单个模式识别受体进化为识别不同的噬菌体编码蛋白。
