Plasticity of Escherichia coli cell wall metabolism promotes fitness and antibiotic resistance across environmental conditions

Elizabeth A. Mueller, Alexander J.F. Egan, Eefjan Breukink, Waldemar Vollmer, Petra Anne Levin

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere40754
JournaleLife
Volume8
DOIs
StatePublished - 2019

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