Coordinately regulated interbacterial antagonism defense pathways constitute a bacterial innate immune system

Bacterial survival is fraught with antagonism, including that deriving from viruses and competing bacterial cells^{1–3 4}. It is now appreciated that bacteria mount complex antiviral responses; however, whether a coordinated defense against bacterial threats is undertaken is not well understood. Previously we showed thatPseudomonas aeruginosapossess a danger sensing pathway that is a critical fitness determinant during competition against other bacteria^{5, 6}. Here, we conducted genome-wide screens inP. aeruginosathat reveal three conserved and widespread interbacterial antagonism resistance clusters (arc1-3). We find that althougharc1-3are coordinately activated by the Gac/Rsm danger sensing system, they function independently and provide idiosyncratic defense capabilities, distinguishing them from general stress response pathways. Our findings demonstrate that Arc3 family proteins provide specific protection against phospholipase toxins by preventing the accumulation of lysophospholipids in a manner distinct from previously characterized membrane repair systems. These findings liken the response ofP. aeruginosato bacterial threats to that of eukaryotic innate immunity, wherein threat detection leads to the activation of specialized defense systems.