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

Abstract

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.