1. Immunology and Inflammation
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Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

  1. Mark Austin Hanson  Is a corresponding author
  2. Anna Dostálová
  3. Camilla Ceroni
  4. Mickael Poidevin
  5. Shu Kondo
  6. Bruno Lemaître  Is a corresponding author
  1. École Polytechnique Fédérale de Lausanne, Switzerland
  2. Université Paris-Saclay, France
  3. National Institute of Genetics, Japan
Research Article
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Cite this article as: eLife 2019;8:e44341 doi: 10.7554/eLife.44341
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Abstract

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilised CRISPR gene editing to delete all known immune inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

Data availability

Data generated or analysed during this study are included in the manuscript and supporting files. Source data has been provided for Figure 2.

Article and author information

Author details

  1. Mark Austin Hanson

    Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    mark.hanson@epfl.ch
    Competing interests
    No competing interests declared.
  2. Anna Dostálová

    Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    No competing interests declared.
  3. Camilla Ceroni

    Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    No competing interests declared.
  4. Mickael Poidevin

    Institute for Integrative Biology of the Cell, Université Paris-Saclay, Gif-sur-Yvette, France
    Competing interests
    No competing interests declared.
  5. Shu Kondo

    Genetic Strains Research Center, National Institute of Genetics, Mishima, Japan
    Competing interests
    No competing interests declared.
  6. Bruno Lemaître

    Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    For correspondence
    bruno.lemaitre@epfl.ch
    Competing interests
    Bruno Lemaître, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7970-1667

Funding

The authors declare that there was no funding for this work

Reviewing Editor

  1. Andrew J MacPherson, University of Bern, Switzerland

Publication history

  1. Received: December 12, 2018
  2. Accepted: February 13, 2019
  3. Accepted Manuscript published: February 26, 2019 (version 1)
  4. Version of Record published: March 4, 2019 (version 2)
  5. Version of Record updated: May 28, 2019 (version 3)

Copyright

© 2019, Hanson 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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