TY - JOUR TI - Plasticity of Escherichia coli cell wall metabolism promotes fitness and antibiotic resistance across environmental conditions AU - Mueller, Elizabeth A AU - Egan, Alexander JF AU - Breukink, Eefjan AU - Vollmer, Waldemar AU - Levin, Petra Anne A2 - Laub, Michael T A2 - Storz, Gisela A2 - Laub, Michael T VL - 8 PY - 2019 DA - 2019/04/09 SP - e40754 C1 - eLife 2019;8:e40754 DO - 10.7554/eLife.40754 UR - https://doi.org/10.7554/eLife.40754 AB - Although the peptidoglycan cell wall is an essential structural and morphological feature of most bacterial cells, the extracytoplasmic enzymes involved in its synthesis are frequently dispensable under standard culture conditions. By modulating a single growth parameter—extracellular pH—we discovered a subset of these so-called ‘redundant’ enzymes in Escherichia coli are required for maximal fitness across pH environments. Among these pH specialists are the class A penicillin binding proteins PBP1a and PBP1b; defects in these enzymes attenuate growth in alkaline and acidic conditions, respectively. Genetic, biochemical, and cytological studies demonstrate that synthase activity is required for cell wall integrity across a wide pH range and influences pH-dependent changes in resistance to cell wall active antibiotics. Altogether, our findings reveal previously thought to be redundant enzymes are instead specialized for distinct environmental niches. This specialization may ensure robust growth and cell wall integrity in a wide range of conditions. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). KW - redundancy KW - penicillin binding proteins KW - pH KW - Peptidoglycan KW - beta-lactam antibiotics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -