PT - JOURNAL ARTICLE AU - S. M. Nayeemul Bari AU - Lucy Chou-Zheng AU - Olivia Howell AU - Katie Cater AU - Vidya Sree Dandu AU - Alexander Thomas AU - Barbaros Aslan AU - Asma Hatoum-Aslan TI - A unique mode of nucleic acid immunity performed by a single multifunctional enzyme AID - 10.1101/776245 DP - 2021 Jan 01 TA - bioRxiv PG - 776245 4099 - http://biorxiv.org/content/early/2021/08/30/776245.short 4100 - http://biorxiv.org/content/early/2021/08/30/776245.full AB - The perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve anti-phage defense. However, the prevalence and effectiveness of much simpler, single-component systems that cleave DNA remain unknown. Here, we describe a novel mode of nucleic acid immunity performed by a single enzyme with nuclease and helicase activities, herein referred to as Nhi. This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi acts as both the sensor and effector to degrade phage-specific replication intermediates.Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in anti-phage defense.Competing Interest StatementThe authors have declared no competing interest.