DEPENDENCE OF PEPTIDOGLYCAN METABOLISM ON PHOSPHOLIPID-SYNTHESIS DURING GROWTH OF ESCHERICHIA-COLI

The role of phospholipid synthesis in peptidoglycan metabolism during growth of Escherichia coil was determined. The inhibition of phospholi pid synthesis, achieved by inhibiting fatty acid synthesis with cerule nin or by glycerol deprivation of gpsA mutant strains, resulted in the concomitant inhibition of peptidoglycan synthesis. These effects on p eptidoglycan synthesis were relatively specific in that the treatments did not cause a general inhibition of macromolecular synthesis. Furth ermore, the inhibition of phospholipid synthesis also resulted in the rapid development of penicillin tolerance. It was unlikely that penici llin tolerance in these cases were simply due to the inhibition of gro wth caused by cerulenin treatment or glycerol deprivation because trea tments with more effective growth inhibitors, e.g. chloramphenicol or norfloxacin, did not confer penicillin tolerance. Penicillin tolerance was shown to be a direct consequence of the inhibition of phospholipi d synthesis and not due to the possible accumulation of guanosine-3',5 '-bispyrophosphate (ppGpp), the starvation stress signal molecule know n to be responsible for the development of penicillin tolerance in ami no-acid-deprived bacteria. Therefore, peptidoglycan metabolism is coup led to phospholipid synthesis during growth of E. coil, and this may r epresent an important means to ensure the coordination of cell envelop e synthesis in growing bacteria.