Organisms spanning all domains of life protect against pathogens using diverse 7 mechanisms of nucleic acid immunity which detect and eliminate foreign genetic 8 material 1 . The perpetual arms race between bacteria and their viruses (phages) has given 9 rise to both innate and adaptive nucleic acid immunity mechanisms, including 10 restriction-modification and CRISPR-Cas, respectively 2 . These sophisticated systems 11 encode multiple components that sense and degrade phage-derived genetic material 12 while leaving the host genome unharmed. Here, we describe a unique mode of innate 13 immunity performed by a single protein, SERP2475, herein renamed to Nhi. We show that 14 this enzyme protects against phages by preventing phage DNA accumulation, and in a 15 purified system it degrades both DNA and RNA substrates. This enzyme also exhibits 16 ATP-dependent helicase activity, and excess ATP abrogates nuclease function, 17 suggesting a possible mechanism for its regulation. Further, using directed evolution, we 18 isolated and characterized a collection of resistant phage mutants and found that a 19 single-stranded DNA binding protein provides a natural means for phages to escape 20 immunity. These observations support a model in which Nhi senses and degrades 21 phage-specific replication intermediates. We also found that this dual-function enzyme 22 protects against diverse phages, and its homologs are distributed across several 23 bacterial phyla. Altogether, our findings reveal a new innate immune system with minimal 24 composition that provides robust defense against diverse bacterial viruses. a process that typically leads to the death of the host (Fig. 1a). In response, bacteria have 30 evolved diverse immune systems that target nearly every step of the phage infection cycle 2 --31 such systems may block phage genome entry, digest phage-derived nucleic acids, and/or 32 initiate programmed cell death, a process known as abortive infection (Abi), to prevent the 33 spread of a phage infection. Perhaps the most direct mechanism to block phage replication is 34 through the use of nucleases that sense and destroy foreign genetic material. However, bacteria 35 are known to possess only two modes of nucleic acid immunity which contribute to anti-phage 36 defense: Innate immunity provided by restriction-modification (R-M) and adaptive immunity 37 conferred by CRISPR-Cas ( Fig. 1a). Given that bacteria and their phages have been co-38 evolving for billions of years, it is only natural to expect that many unknown immune systems 39 are yet to be discovered, particularly in non-model organisms 4,5 . 40Here, we sought to identify and characterize new anti-phage immune mechanisms in the 41 commensal opportunistic pathogen Staphylococcus epidermidis RP62a 6 . This organism encodes 42 a Type III-A CRISPR-Cas system 7 , an Abi mechanism 8 , and a putative Type I R-M system 43 (GenBank Accession CP000029.1). All three systems reside within ~30,000 nucleotides of each 44 other (Extended Data 1a), in agreement with recent evidence...