Metabolite profiling and peptidoglycan analysis of transient cell wall-deficient bacteria in a new Escherichia coli model system

Environ Microbiol. 2015 May;17(5):1586-99. doi: 10.1111/1462-2920.12594. Epub 2014 Sep 22.

Abstract

Many bacteria are able to assume a transient cell wall-deficient (or L-form) state under favourable osmotic conditions. Cell wall stress such as exposure to β-lactam antibiotics can enforce the transition to and maintenance of this state. L-forms actively proliferate and can return to the walled state upon removal of the inducing agent. We have adopted Escherichia coli as a model system for the controlled transition to and reversion from the L-form state, and have studied these dynamics with genetics, cell biology and 'omics' technologies. As such, a transposon mutagenesis screen underscored the requirement for the Rcs phosphorelay and colanic acid synthesis, while proteomics show only little differences between rods and L-forms. In contrast, metabolome comparison reveals the high abundance of lysophospholipids and phospholipids with unsaturated or cyclopropanized fatty acids in E. coli L-forms. This increase of membrane lipids associated with increased membrane fluidity may facilitate proliferation through bud formation. Visualization of the residual peptidoglycan with a fluorescently labelled peptidoglycan binding protein indicates de novo cell wall synthesis and a role for septal peptidoglycan synthesis during bud constriction. The DD-carboxypeptidases PBP5 and PBP6 are threefold and fourfold upregulated in L-forms, indicating a specific role for regulation of crosslinking during L-form proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall / metabolism*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / genetics
  • Gene Library
  • Membrane Lipids / metabolism*
  • Models, Biological
  • Penicillin-Binding Proteins / biosynthesis
  • Penicillin-Binding Proteins / genetics
  • Peptidoglycan / metabolism*
  • Serine-Type D-Ala-D-Ala Carboxypeptidase / biosynthesis
  • Serine-Type D-Ala-D-Ala Carboxypeptidase / genetics
  • beta-Lactam Resistance / genetics
  • beta-Lactams / pharmacology

Substances

  • Escherichia coli Proteins
  • Membrane Lipids
  • PBP5 protein, E coli
  • Penicillin-Binding Proteins
  • Peptidoglycan
  • beta-Lactams
  • DacC protein, E coli
  • Serine-Type D-Ala-D-Ala Carboxypeptidase