A potential role for acyl-phosphate in the coordination of phospholipid and lipopolysaccharide synthesis in Escherichia coli
The envelope of Gram-negative bacteria like Escherichia coli is multilayered with two membranessandwiching a peptidoglycan cell wall. The inner membrane is a typical phospholipid bilayerwhereas the outer membrane is asymmetric with phospholipids in the inner leaflet andlipopolysaccharide (LPS) in the outer leaflet. We recently discovered that inactivation of theconserved peptidoglycan synthesis machinery responsible for cell elongation causes defects inboth peptidoglycan and LPS synthesis in E. coli. This finding suggests that the isolation ofsuppressors that rescue the growth phenotype caused by an impaired cell elongation system isan attractive means of identifying factors involved in coordinating the biogenesis of differentenvelope layers. Here, we report the results of a global, transposon sequencing-based screenfor such suppressors. The inactivation of a number of factors including the phospholipid synthesisenzyme PlsX was found to partially suppress the growth defects of a cell elongation mutant.Deletion of plsX also conferred increased resistance to CHIR-090, an inhibitor of the committedstep of LPS synthesis catalyzed by LpxC, suggesting that loss of PlsX function stimulates LPSsynthesis. Evidence is presented that increased CHIR-090 resistance is not mediated by changesin the activity of the proteolytic system (YejM-LapB-FtsH) controlling LpxC turnover. Rather, ourresults are consistent with a model in which the phospholipid precursor acyl-phosphate producedby PlsX serves as an inhibitor of LpxC to lower the rate of LPS synthesis when phospholipidsynthesis capacity is reduced.