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Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

View ORCID ProfileM.A. Hanson, A. Dostálová, C. Ceroni, M. Poidevin, View ORCID ProfileS. Kondo, View ORCID ProfileB. Lemaitre
doi: https://doi.org/10.1101/493817
M.A. Hanson
1Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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  • For correspondence: mark.hanson@epfl.ch bruno.lemaitre@epfl.ch
A. Dostálová
1Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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C. Ceroni
1Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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M. Poidevin
2Institute for Integrative Biology of the Cell, Université Paris-Saclay, CEA, CNRS, Université Paris Sud, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
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S. Kondo
3Invertebrate Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, Mishima, Japan
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B. Lemaitre
1Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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  • For correspondence: mark.hanson@epfl.ch bruno.lemaitre@epfl.ch
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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, acting 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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 13, 2018.
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Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
M.A. Hanson, A. Dostálová, C. Ceroni, M. Poidevin, S. Kondo, B. Lemaitre
bioRxiv 493817; doi: https://doi.org/10.1101/493817
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Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
M.A. Hanson, A. Dostálová, C. Ceroni, M. Poidevin, S. Kondo, B. Lemaitre
bioRxiv 493817; doi: https://doi.org/10.1101/493817

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