Cell density-dependent death triggered by viral palindromic DNA sequences

Defense systems that recognize viruses have provided not only the tools of molecular biology but also important insights into other mechanisms that can induce immunity to these or other infectious agents including transmissible plasmids and chromosomal genetic elements. Several systems that trigger cell death upon viral infection have recently been recognized but the signals that activate these abortive infection systems remain largely unknown. Here we characterize one such system in Vibrio cholerae that we found was responsible for triggering cell-density dependent death (CDD) of bacterial cells in response to the presence of certain genetic elements. The key components of the CDD system include quorum-regulated components DdmABC and the host factor PriA. Our analysis indicates that the plasmid and phage signals that trigger CDD were palindromic DNA sequences that are predicted to form stem-loop hairpin structures from single-stranded DNA during stalled replication. Our results further suggest that other agents that generate damaged DNA can also trigger DdmABC/PriA activation and cell death probably through activation of a nuclease domain present in the DdmA protein. Thus, any infectious process that results in damaged DNA, particularly during DNA replication, can in theory trigger cell death through the DdmABC/PriA abortive infection system.