Dead‐end intermediates in the enterobacterial common antigen pathway induce morphological defects in Escherichia coli by competing for undecaprenyl phosphate

Summary Bacterial morphology is determined primarily by the architecture of the peptidoglycan (PG) cell wall, a mesh‐like layer that encases the cell. To identify novel mechanisms that create or maintain cell shape in Escherichia coli, we used flow cytometry to screen a transposon insertion library and identified a wecE mutant that altered cell shape, causing cells to filament and swell. WecE is a sugar aminotransferase involved in the biosynthesis of enterobacterial common antigen (ECA), a non‐essential outer membrane glycolipid of the Enterobacteriaceae. Loss of wecE interrupts biosynthesis of ECA and causes the accumulation of the undecaprenyl pyrophosphate‐linked intermediate ECA‐lipid II. The wecE shape defects were reversed by: (i) preventing initiation of ECA biosynthesis, (ii) increasing the synthesis of the lipid carrier undecaprenyl phosphate (Und‐P), (iii) diverting Und‐P to PG synthesis or (iv) promoting Und‐P recycling. The results argue that the buildup of ECA‐lipid II sequesters part of the pool of Und‐P, which, in turn, adversely affects PG synthesis. The data strongly suggest there is competition for a common pool of Und‐P, whose proper distribution to alternate metabolic pathways is required to maintain normal cell shape in E. coli. Undecaprenyl‐phosphate (Und‐P) is a key bacterial compound used to synthesize several glycan polymers, including cell wall peptidoglycan. Mutants that truncate the enterobacterial common antigen pathway accumulate dead‐end intermediates that sequester Und‐P and restrict its availability for synthesizing peptidoglycan, the primary determinant of cell shape. The results indicate that a common pool of Und‐P must be distributed carefully among various metabolic pathways if cells are to maintain normal growth and morphology.