Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Division of Microbial Ecology, Center for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria.
Nat Microbiol. 2022 Nov;7(11):1849-1856. doi: 10.1038/s41564-022-01207-8. Epub 2022 Oct 3.
Defence-associated sirtuins (DSRs) comprise a family of proteins that defend bacteria from phage infection via an unknown mechanism. These proteins are common in bacteria and harbour an N-terminal sirtuin (SIR2) domain. In this study we report that DSR proteins degrade nicotinamide adenine dinucleotide (NAD) during infection, depleting the cell of this essential molecule and aborting phage propagation. Our data show that one of these proteins, DSR2, directly identifies phage tail tube proteins and then becomes an active NADase in Bacillus subtilis. Using a phage mating methodology that promotes genetic exchange between pairs of DSR2-sensitive and DSR2-resistant phages, we further show that some phages express anti-DSR2 proteins that bind and repress DSR2. Finally, we demonstrate that the SIR2 domain serves as an effector NADase in a diverse set of phage defence systems outside the DSR family. Our results establish the general role of SIR2 domains in bacterial immunity against phages.
防御相关的沉默调节蛋白（DSRs）构成了一个蛋白家族，通过未知机制来保护细菌免受噬菌体感染。这些蛋白在细菌中很常见，并且含有一个 N 端的沉默调节蛋白（SIR2）结构域。在这项研究中，我们报告说 DSR 蛋白在感染过程中降解烟酰胺腺嘌呤二核苷酸（NAD），耗尽细胞中这种必需分子并终止噬菌体的繁殖。我们的数据表明，这些蛋白中的一种，DSR2，直接识别噬菌体尾部管蛋白，然后在枯草芽孢杆菌中成为一种活性 NAD 酶。使用一种促进 DSR2 敏感和 DSR2 抗性噬菌体之间遗传交换的噬菌体交配方法，我们进一步表明，一些噬菌体表达了抗 DSR2 蛋白，这些蛋白结合并抑制 DSR2。最后，我们证明 SIR2 结构域在 DSR 家族之外的多种噬菌体防御系统中充当效应 NAD 酶。我们的结果确立了 SIR2 结构域在细菌抵御噬菌体中的普遍作用。
