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

Bacterial cells live under constant existential threats imposed by other bacteria and viruses. Mechanisms for contending with these threats are well documented; however, the regulation of these diverse defense elements remains poorly understood. Here, we describe a genome-wide, coordinated, and highly effective immune response, termed Gac/Rsm-regulated unified antagonism response and defense (GUARD), that protects against bacterial and viral threats using a single regulatory pathway. Bioinformatic analyses reveal a Pseudomonas-wide form of the Gac/Rsm regulatory pathway (GRP), an established danger-sensing system in P. aeruginosa. Proteomic studies of diverse Pseudomonas species show that the pathway regulates a large and variable suite of factors implicated in defense against both bacterial and phage threats. Focusing on P. protegens, we identify profound phenotypic consequences of these factors against multiple forms of bacterial antagonism and several phages. Together, our results reveal that bacteria, like multicellular eukaryotes, couple danger sensing to the activation of an immune response with antibacterial and antiviral arms.