FIG 6 .

Pathway of stringent response with relA hydrolase mutation. During stress response, RelA (RSH/SpoT homolog in VRE) and RelQ are responsible for the production of the alarmone (red circles). In the relA mutants, a missense mutation adjacent to an active site in the hydrolysis domain led to increased resting levels of ppGpp. Cells were “primed” to respond faster to stress in a biofilm, which included antibiotic stress in the patient’s case. We propose that the presence of ppGpp downregulated multiple nonessential pathways, as shown by the RNA-seq data, including biofilm components. Therefore, while the relA mutant was fit to survive in an immunocompromised patient, once the immune system was reconstituted, the fitness trade-off of a smaller, less robust biofilm would enhance susceptibility to neutrophil killing.