Research Progress on the Sir2 NADase-Mediated Anti-Phage Mechanism in Prokaryotes
ZHANG Wanyue, HUANG Shiqing, LI Guolun, ZHEN Xiangkai, ZHANG Dandan*
Sir2 (silent information regulator 2) domain proteins, as a member of the Sirtuins family of silencing information regulators, exists in various organisms ranging from bacteria to humans. In eukaryotes, the Sir2 domain proteins are NAD+ (nicotinamide adenine dinucleotide)-dependent deacetylases. Functioning as protein deacetylases or ADP ribonucleotide transferases, they are involved in regulating transcriptional repression, gene recombination, DNA repair, and the cell cycle process. Recent research has revealed that proteins containing the Sir2 domain are extensively distributed in multiple microbial immune systems in prokaryotes and act as NAD hydrolases, namely NADases. When bacteria are infected by phages, they can rapidly hydrolyze NAD+ within the bacteria, thereby causing the death of the infected bacteria. Studies have shown that defense systems such as Thoeris, SPARSA, Sir2-HerA, DSR2, and Kongming all function through the Sir2-dependent NADases. This review mainly introduces these five anti-phage defense systems and discusses the crucial role of the Sir2 domain in phage defense, providing theoretical support for an in-depth understanding of the prokaryotic Sir2 NADase-mediated anti-phage mechanism.