ROLE OF PRECURSOR TRANSLOCATION IN COORDINATION OF MUREIN AND PHOSPHOLIPID-SYNTHESIS IN ESCHERICHIA-COLI

Inhibition of phospholipid synthesis in Escherichia coli by either cer ulenin treatment or glycerol starvation of a glycerol-auxotrophic muta nt resulted in a concomitant block of murein synthesis, The intracellu lar pool of cytoplasmic and lipid-linked murein precursors was not aff ected by an inhibition of phospholipid synthesis, nor was the activity of the penicillin-binding proteins, In addition, a decrease in the ac tivity of the two lipoprotein murein hydrolases, the lytic transglycos ylases A and B, could not be demonstrated. The indirect inhibition of murein synthesis by cerulenin resulted in a 68% decrease of trimeric m uropeptide structures, proposed to represent the attachment points of newly added murein, Importantly, inhibition of phospholipid synthesis also inhibited O-antigen synthesis with a sensitivity and kinetics sim ilar to those of murein synthesis, It is concluded that the step commo n for murein and O-antigen synthesis, the translocation of the respect ive bactoprenolphosphate-linked precursor molecules, is affected by an inhibition of phospholipid synthesis, Consistent with this assumption , it was shown that murein synthesis no longer depends on ongoing phos pholipid synthesis in ether-permeabilized cells, We propose that the a ssembly of a murein-synthesizing machinery, a multienzyme complex cons isting of murein hydrolases and synthases, at specific sites of the me mbrane, where integral membrane proteins such as RodA and FtsW facilit ate the translocation of the lipid-linked murein precursors to the per iplasm, depends on ongoing phospholipid synthesis, This would explain the well-known phenomenon that both murein synthesis and antibiotic-in duced autolysis depend on phospholipid synthesis and thereby indirectl y on the stringent control.