Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system

  1. Christopher Icke
  2. Freya J Hodges
  3. Karthik Pullela
  4. Samantha A McKeand
  5. Jack Alfred Bryant
  6. Adam F Cunningham
  7. Jeff A Cole
  8. Ian R Henderson  Is a corresponding author
  1. University of Birmingham, United Kingdom
  2. University of Queensland, Australia

Abstract

Protein acylation is critical for many cellular functions across all domains of life. In bacteria, lipoproteins have important roles in virulence and are targets for the development of antimicrobials and vaccines. Bacterial lipoproteins are secreted from the cytosol via the Sec pathway and acylated on an N-terminal cysteine residue through the action of three enzymes. In Gram-negative bacteria, the Lol pathway transports lipoproteins to the outer membrane. Here we demonstrate that the Aat secretion system is a composite system sharing similarity with elements of a type I secretion systems and the Lol pathway. During secretion, the AatD subunit acylates the substrate CexE on a highly conserved N-terminal glycine residue. Mutations disrupting glycine acylation interfere with membrane incorporation and trafficking. Our data reveal CexE as the first member of a new class of glycine-acylated lipoprotein, while Aat represents a new secretion system that displays the substrate lipoprotein on the cell surface.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Christopher Icke

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7815-8591
  2. Freya J Hodges

    Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Karthik Pullela

    Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Samantha A McKeand

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Jack Alfred Bryant

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7912-2144
  6. Adam F Cunningham

    Institute of Microbiology and Infection, Institute of Inflammation and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Jeff A Cole

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Ian R Henderson

    Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    For correspondence
    i.henderson@imb.uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9954-4977

Funding

Biotechnology and Biological Sciences Research Council (DTP)

  • Adam F Cunningham
  • Ian R Henderson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Petra Anne Levin, Washington University in St. Louis, United States

Publication history

  1. Received: October 6, 2020
  2. Accepted: February 23, 2021
  3. Accepted Manuscript published: February 24, 2021 (version 1)
  4. Version of Record published: March 8, 2021 (version 2)

Copyright

© 2021, Icke 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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  1. Christopher Icke
  2. Freya J Hodges
  3. Karthik Pullela
  4. Samantha A McKeand
  5. Jack Alfred Bryant
  6. Adam F Cunningham
  7. Jeff A Cole
  8. Ian R Henderson
(2021)
Glycine acylation and trafficking of a new class of bacterial lipoprotein by a composite secretion system
eLife 10:e63762.
https://doi.org/10.7554/eLife.63762
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