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

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 concentrati...

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Bibliographic Details
Main Authors: Mark Austin Hanson, Anna Dostálová, Camilla Ceroni, Mickael Poidevin, Shu Kondo, Bruno Lemaitre
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2019-02-01
Series:eLife
Subjects:
AMP
Imd
Online Access:https://elifesciences.org/articles/44341
Description
Summary: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 utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten 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.
ISSN:2050-084X