biostudies-literatureBrinkley DMNational Institute of Allergy and Infectious DiseasesNIH National Institute of General Medical SciencesHoward Hughes Medical InstituteNIAID NIH HHSUniversity of WashingtonGonzaga UniversityNational Institutes of HealthNIGMS NIH HHS1333-1346.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697246biostudies-literatureUnknown33(8)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 bacteriCell host & microbePseudomonads coordinate innate defense against viruses and bacteria with a single regulatory system.PMC12697246R01 AI0806095R01AI080609T32 GM136534Zhang DBrinkley DMPeterson SBGallagher LATan YMotha de Silva MBertolli SKBrockman AMougous JDfalsePseudomonads 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 bacteri2025-01-01T00:00:00Z2025 Aug2026-06-06T15:35:27.35Z2026-06-02T03:09:03.391ZS-EPMC126972464081218610.1016/j.chom.2025.07.016