RelQ-mediated Alarmone Signaling Regulates Growth, Sporulation, and Stress-induced Biofilm Formation in

The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signaling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in , a biofilm- and spore-forming pathogen that causes resilient, highly recurrent infections. The role of the SR in other processes and the effectors by which it regulates physiology are unknown. RelQ is a clostridial alarmone synthetase. Deletion of dysregulates growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors, and drastically reduces biofilm formation. While wild-type displays increased biofilm formation in the presence of sub-lethal stress, the Δ strain cannot upregulate biofilm production in response to stress. Deletion of slows spore accumulation in planktonic cultures but accelerates it in biofilms. This work establishes biofilm formation and sporulation as alarmone-mediated processes in and reveals the importance of RelQ in stress-induced biofilm regulation.