Activation of a Partial Stringent Response Protects Amino Acid-Deprived Escherichia coli from Ampicillin-Induced Lysis

In amino-acid deprived Escherichia coli ( E. coli ), the activation of the stringent response by RelA and its key alarmone product, guanosine 3’,5’-bispyrophospahte (ppGpp), is necessary for a variety of cellular responses, including tolerance to β -lactam antibiotics such as ampicillin. Ampicillin uncouples the activity of the peptidoglycan polymerases (penicillin-binding proteins) from the hydrolases (autolysins), resulting in the weakening of + the peptidoglycan meshwork. Here, we utilized E. coli strains NF314As19 (wild type relA ), + NF536As19 [ relA valS (Ts)], and NF537As19 [ relA valS (Ts)] as models to study the effects of the stringent response on ampicillin-induced lysis. This report confirmed that the strains behave appropriately by monitoring relative levels of RNA synthesis as an indicator of bacterial growth rate and the induction of the stringent response. This report also demonstrated a protective effect from ampicillin-induced lysis at 37°C produced from partially inactivating the ValS(Ts) protein. These results indicate that a partially activated stringent response in E. coli results in cellular processes that induce a degree of tolerance to ampicillin-induced lysis.