Patel Kishen M, Seed Kimberley D
Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, CA, 94720, United States.
Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, 94720, United States.
Nucleic Acids Res. 2025 Aug 27;53(16). doi: 10.1093/nar/gkaf728.
Bacteria are constantly threatened by their viral predators (phages), which has resulted in the development of defense systems for bacterial survival. One family of defense systems found widely across bacteria are OLD (for overcoming lysogenization defect) family nucleases. Despite recent discoveries regarding Class 2 and 4 OLD family nucleases and how phages overcome them, Class 1 OLD family nucleases remain underexplored, with only one antiphage Class 1 OLD family nuclease described to date. Here, we identify the first bacterially encoded Class 1 OLD family nuclease with antiphage activity: the Vibrio cholerae-encoded Vc OLD. We describe its disruption of genome replication of the lytic vibriophage ICP1. Furthermore, we examine its in vitro activity, identifying Vc OLD as a DNA nickase. Finally, we identify the first direct inhibitor of a Class 1 OLD family nuclease, the ICP1-encoded Oad1. Our research sheds new light on the role of Class 1 OLD family nucleases in phage defense and highlights the dynamic arms race between V. cholerae and its predatory phage ICP1.
细菌不断受到其病毒捕食者（噬菌体）的威胁，这促使细菌进化出防御系统以确保生存。在细菌中广泛发现的一类防御系统是OLD（用于克服溶原化缺陷）家族核酸酶。尽管最近有关于2类和4类OLD家族核酸酶以及噬菌体如何克服它们的发现，但1类OLD家族核酸酶仍未得到充分研究，迄今为止仅描述了一种具有抗噬菌体活性的1类OLD家族核酸酶。在此，我们鉴定出首个具有抗噬菌体活性的细菌编码1类OLD家族核酸酶：霍乱弧菌编码的Vc OLD。我们描述了它对裂解性霍乱弧菌噬菌体ICP1基因组复制的破坏作用。此外，我们检测了它的体外活性，确定Vc OLD是一种DNA切口酶。最后，我们鉴定出首个1类OLD家族核酸酶的直接抑制剂，即ICP1编码的Oad1。我们的研究为1类OLD家族核酸酶在噬菌体防御中的作用提供了新的见解，并突出了霍乱弧菌与其捕食性噬菌体ICP1之间动态的军备竞赛。
