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

ELife
Mark Austin HansonBruno Lemaitre

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 utilized 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.

References

Sep 1, 1993·Journal of Neuroimmunology·H J SchluesenerS Jung
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·B LemaitreJ A Hoffmann
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Uttenweiler-JosephP Bulet
Nov 24, 1999·Insect Biochemistry and Molecular Biology·S Ekengren, D Hultmark
Jan 11, 2000·Biochemical and Biophysical Research Communications·M HedengrenD Hultmark
Apr 17, 2001·Antimicrobial Agents and Chemotherapy·H Yan, R E Hancock
Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sophie RutschmannDominique Ferrandon
Feb 21, 2002·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·S van WeteringP S Hiemstra
Feb 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Phoebe TzouBruno Lemaitre
May 29, 2002·The EMBO Journal·Ennio De GregorioBruno Lemaitre
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·G Sandra TjabringaPieter S Hiemstra
Jan 28, 2004·The Journal of Biological Chemistry·David RabelPhilippe Bulet
Jun 25, 2005·Chemical Immunology and Allergy·Jean-Luc Imler, Philippe Bulet
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sho TokumaruKoji Hashimoto
Apr 19, 2006·Immunity·Anna Zaidman-RémyBruno Lemaitre
Jan 5, 2007·Annual Review of Immunology·Bruno Lemaitre, Jules Hoffmann
Apr 18, 2007·Molecular and Cellular Biology·Takahiro TanjiY Tony Ip
Jul 10, 2008·Current Opinion in Immunology·Michel Gilliet, Roberto Lande
Sep 19, 2008·Molecular Biology and Evolution·Jacob A Tennessen, Michael S Blouin
May 2, 2009·International Journal of Systematic and Evolutionary Microbiology·Punita Juneja, Brian P Lazzaro
May 19, 2009·Nanomedicine : Nanotechnology, Biology, and Medicine·Amanulla Mohammed FayazRamasamy Venketesan
Dec 19, 2009·PLoS Pathogens·Mathilde GendrinBruno Lemaitre
Feb 2, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Eduardo Guaní-GuerraLuis M Terán
Dec 15, 2010·The Journal of Biological Chemistry·Huiwen W ZhaoGabriel G Haddad
Oct 25, 2011·Science·Frédéric H LoginAbdelaziz Heddi

❮ Previous
Next ❯

Citations

May 13, 2020·ELife·Sudhir Gopal TattikotaNorbert Perrimon
Sep 1, 2020·PLoS Pathogens·Saleem AlamehMikhail Martchenko Shilman
May 14, 2019·Genes & Nutrition·Nieves Baenas, Anika E Wagner
Oct 28, 2019·PloS One·Moria Cairns ChambersBrian P Lazzaro
Feb 11, 2020·Frontiers in Immunology·Lianne B CohenSteven A Wasserman
May 6, 2019·Viruses·Cara WestNeal Silverman
Apr 25, 2019·International Journal of Molecular Sciences·Alan V Nguyen, Athena M Soulika
Jan 31, 2020·Frontiers in Immunology·Samuel J H LinSteven A Wasserman
Mar 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Igor IatsenkoBruno Lemaitre
May 20, 2020·Frontiers in Immunology·Marco GerdolDelphine Destoumieux-Garzón
Apr 10, 2020·Frontiers in Immunology·Tiina S Salminen, Pedro F Vale
Feb 29, 2020·Nature Reviews. Drug Discovery·Neeloffer MookherjeeDonald J Davidson
Feb 11, 2020·Frontiers in Immunology·Saeideh Davoodi, Edan Foley
Feb 2, 2021·Chemical Reviews·Jasmin PortelinhaAlfredo M Angeles-Boza
Feb 5, 2021·Frontiers in Cellular and Infection Microbiology·Agustín RolandelliAlessandra A Guarneri
Dec 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Verónica RojasFanny Guzmán
Dec 5, 2020·Scientific Reports·Francisco J SilvaAmparo Latorre
Jul 3, 2021·Insects·Patrycja SkowronekAneta Strachecka
Oct 28, 2020·The Journal of Physical Chemistry Letters·Jacob M RemingtonJianing Li
May 2, 2020·Science·Brian P LazzaroJens Rolff

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
FACS
dissection
PCR

Software Mentioned

Prism
Leica Application Suite
R

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.