Pseudomonads coordinate innate defense against viruses and bacteria with a single regulatory system.

Bacterial cells live under the constant existential threats imposed by other bacteria and viruses. Their mechanisms for contending with these threats are well documented; however, the regulation of these diverse defense elements remains poorly understood. Here we show that bacteria can mount a genome-wide, coordinated, and highly effective immune response against bacterial and viral threats using a single regulatory pathway. Bioinformatic analyses revealed that species broadly possess a specialized form of the Gac/Rsm regulatory pathway (GRP), which our prior work in implicated in activating interbacterial antagonism defense mechanisms in response to neighbor cell death. Proteomic studies comparing GRP-activated and -inactivated strains derived from diverse species showed that the pathway regulates a large and variable suite of factors implicated in defense against both bacterial and phage threats. Focusing on we identify profound phenotypic consequences of these factors against multiple forms of bacterial antagonism and several phage. Together, our results reveal that bacteria, like more complex organisms, couple danger sensing to the activation of an immune system with antibacterial and antiviral arms.