1. Microbiology and Infectious Disease
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A mutant Escherichia coli that attaches peptidoglycan to lipopolysaccharide and displays cell wall on its surface

  1. Marcin Grabowicz
  2. Dorothee Andres
  3. Matthew D Lebar
  4. Goran Malojčić
  5. Daniel Kahne
  6. Thomas J Silhavy  Is a corresponding author
  1. Princeton University, United States
  2. Harvard University, United States
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Cite this article as: eLife 2014;3:e05334 doi: 10.7554/eLife.05334

Abstract

The lipopolysaccharide (LPS) forms the surface-exposed leaflet of the outer membrane (OM) of Gram-negative bacteria, an organelle that shields the underlying peptidoglycan (PG) cell wall. Both LPS and PG are essential cell envelope components that are synthesized independently and assembled by dedicated transenvelope multiprotein complexes. We have identified a point-mutation in the gene for O-antigen ligase (WaaL) in Escherichia coli that causes LPS to be modified with PG subunits, intersecting these two pathways. Synthesis of the PG-modified LPS (LPS*) requires ready access to the small PG precursor pool but does not weaken cell wall integrity, challenging models of precursor sequestration at PG assembly machinery. LPS* is efficiently transported to the cell surface without impairing OM function. Because LPS* contains the canonical vancomycin binding site, these surface- exposed molecules confer increased vancomycin-resistance by functioning as molecular decoys that titrate the antibiotic away from its intracellular target. This unexpected LPS glycosylation fuses two potent pathogen-associated molecular patterns (PAMPs).

Article and author information

Author details

  1. Marcin Grabowicz

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dorothee Andres

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew D Lebar

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Goran Malojčić

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel Kahne

    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Thomas J Silhavy

    Department of Molecular Bioloy, Princeton University, Princeton, United States
    For correspondence
    tsilhavy@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Eduardo A Groisman, Yale University/HHMI, United States

Publication history

  1. Received: October 29, 2014
  2. Accepted: December 24, 2014
  3. Accepted Manuscript published: December 31, 2014 (version 1)
  4. Version of Record published: January 17, 2015 (version 2)

Copyright

© 2014, Grabowicz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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