BETA-LACTAM-INDUCED BACTERIOLYSIS OF AMINO ACID-DEPRIVED ESCHERICHIA-COLI IS DEPENDENT ON PHOSPHOLIPID-SYNTHESIS

The penicillin tolerance of amino acid-deprived reLA(+) Escherichia co il is attributed to the stringent response; i.e., relaxation of the st ringent response suppresses penicillin tolerance. The beta-lactam-indu ced lysis of amino acid-deprived bacteria resulting from relaxation of the stringent response was inhibited by cerulenin, or by glycerol dep rivation in the case of a gpsA mutant (defective in the biosynthetic s n-glycerol 3-phosphate dehydrogenase). Therefore, beta-lactam-induced lysis of amino acid-deprived cells was dependent on phospho lipid synt hesis. The lysis process during amino acid deprivation can be experime ntally dissociated into two stages designated the priming stage (durin g which the interaction between the beta-lactam and the penicillin-bin ding proteins occurs) and the beta-lactam-independent lysis induction stage. Both stages were shown to require phospholipid synthesis. It ha s been known for some time that the inhibition of phospholipid synthes is is among the plethora of physiological changes resulting from the s tringent response. These results indicate that the inhibition of pepti doglycan synthesis and the penicillin tolerance associated with the st ringent response are both secondary consequences of the inhibition of phospholipid synthesis.