YprA-family helicases provide the missing link between diverse prokaryotic immune systems.

Bacteria and archaea possess an enormous variety of antiviral immune systems that often share homologous proteins and domains. YprA-family helicases are central to widespread defense systems, which include defense island system associated with restriction-modification (DISARM), 7-deazapurine in DNA (Dpd), and Druantia. Through comprehensive phylogenetic and structural analyses of YprA-like helicases, we identify several major clades, which define distinct defense systems including a broad class we call ARMADA (disARM-related antiviral defense array). Apart from the YprA-like helicase, ARMADAs share two more proteins with DISARM, but their YprA homologs are most similar to those of Druantia, which suggests that ARMADA is a missing link connecting DISARM and Druantia. We show experimentally that ARMADA protects bacteria against a broad range of phages via a direct, non-abortive mechanism. We further demonstrate that ARMADA and Druantia Type III systems often co-occur within distinct satellite phage-like mobile elements, which we call SPIDERs (satellite phage integrated defensive and ecotypic replicons) and which provide synergistic resistance against diverse phages.