Inhibition of
phospholipid synthesis in Escherichia coli by either
cerulenin treatment or
glycerol starvation of a
glycerol-auxotrophic mutant resulted in a concomitant block of
murein synthesis. The intracellular pool of cytoplasmic and
lipid-linked
murein precursors was not affected by an inhibition of
phospholipid synthesis, nor was the activity of the
penicillin-binding proteins. In addition, a decrease in the activity of the two
lipoprotein murein hydrolases, the lytic transglycosylases A and B, could not be demonstrated. The indirect inhibition of
murein synthesis by
cerulenin resulted in a 68% decrease of trimeric muropeptide 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 similar to those of
murein synthesis. It is concluded that the step common for
murein and
O-antigen synthesis, the translocation of the respective 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
phospholipid synthesis in
ether-permeabilized cells. We propose that the assembly of a
murein-synthesizing machinery, a multienzyme complex consisting of
murein hydrolases and synthases, at specific sites of the membrane, where
integral membrane proteins such as RodA and FtsW facilitate the translocation of the
lipid-linked
murein precursors to the periplasm, depends on ongoing
phospholipid synthesis. This would explain the well-known phenomenon that both
murein synthesis and
antibiotic-induced
autolysis depend on
phospholipid synthesis and thereby indirectly on the stringent control.