Abstract
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 lysogeny defect) family nucleases. Despite recent discoveries regarding Class 2 and 4 OLD family nucleases and how phages overcome them, Class 1 OLD family nucleases warrant further study as there has only been one anti-phage Class 1 OLD family nuclease described to date. Here, we identify the Vibrio cholerae-encoded Class 1 OLD family nuclease Vc OLD and 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 further illuminates Class 1 OLD family nucleases' role in phage defense and explores the dynamic arms race between V. cholerae and its predatory phage ICP1.