Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion
Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion
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DOI：
10.1038/s41564-022-01207-8
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发表时间：
2022-10-03
影响因子：
28.3
通讯作者：
Sorek, Rotem
中科院分区：
文献类型：
--
作者：
Garb, Jeremy;Lopatina, Anna;Sorek, Rotem
防御相关沉默调节蛋白（Defence associated sirtuins，DSRs）是一类通过未知机制保护细菌免受噬菌体感染的蛋白质家族。这些蛋白质在细菌中很常见，并含有N-末端sirtuin（SIR 2）结构域。在这项研究中，我们报告DSR蛋白降解烟酰胺腺嘌呤二核苷酸（NAD（+））在感染过程中，消耗这种必需的分子和中止噬菌体繁殖的细胞。我们的数据表明，这些蛋白之一，DSR 2，直接识别噬菌体尾管蛋白，然后成为一个活跃的NAD酶在枯草芽孢杆菌。使用噬菌体交配方法，促进对DSR 2敏感和DSR 2抗性的细菌之间的遗传交换，我们进一步表明，一些细菌表达抗DSR 2蛋白，结合和抑制DSR 2。最后，我们证明了SIR 2结构域在DSR家族以外的一组不同的噬菌体防御系统中作为效应子NAD酶。我们的研究结果建立了SIR 2结构域在细菌抗SPR噬菌体免疫中的一般作用。来自枯草芽孢杆菌的含SIR 2结构域的蛋白DSR 2通过NAD（+）耗竭来保护免受SPR噬菌体感染。一些大肠杆菌表达抗DSR 2蛋白，阻断细菌免疫。
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.The SIR2-domain-containing protein DSR2 from Bacillussubtilis protects against SPR phage infection via NAD(+) depletion. Some phages express anti-DSR2 proteins, blocking bacterial immunity.