Bacteria employ a variety of systems to protect themselves against the phages that infect them. We previously identified a new phage defense system, called Hna, in the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti. Hna protects against phages from both the Myoviridae and Podoviridae families, and an Hna homologue from Escherichia coli confers protection against several well-studied E. coli phages, including T7, T4, and the lambdoid phage HK97. The Hna system consists of a single predicted superfamily 2 helicase/nuclease protein that acts via an abortive infection mechanism, meaning that its prevention of phage replication leads to cell death. In an effort to identify how Hna senses phage infection, we isolated “escape” mutant phages that can replicate in cells with Hna. These escape phages carry mutations in a single-stranded DNA binding protein (SSB). We show that expression of this SSB is sufficient to provoke a host abortive infection response in cells carrying Hna, independent of phage infection. We are now characterizing the molecular mechanism by which Hna causes abortive infection and are searching for other “activators” of Hna from other phages. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assays indicate that host DNA damage occurs when Hna is activated by phage SSB, suggesting that Hna may cause cell death by cleaving the host genome.