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In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics

Oligomerization of antimicrobial peptides into nanosized supramolecular complexes produced in biological systems (inclusion bodies and self-assembling nanoparticles) seems an appealing alternative to conventional antibiotics. In this work, the antimicrobial peptide, GWH1, was N-terminally fused to t...

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Autores principales: Carratalá, Jose V., Brouillette, Eric, Serna, Naroa, Sánchez-Chardi, Alejandro, Sánchez, Julieta M., Villaverde, Antonio, Arís, Anna, Garcia-Fruitós, Elena, Ferrer-Miralles, Neus, Malouin, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766456/
https://www.ncbi.nlm.nih.gov/pubmed/33348529
http://dx.doi.org/10.3390/pharmaceutics12121217
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author Carratalá, Jose V.
Brouillette, Eric
Serna, Naroa
Sánchez-Chardi, Alejandro
Sánchez, Julieta M.
Villaverde, Antonio
Arís, Anna
Garcia-Fruitós, Elena
Ferrer-Miralles, Neus
Malouin, François
author_facet Carratalá, Jose V.
Brouillette, Eric
Serna, Naroa
Sánchez-Chardi, Alejandro
Sánchez, Julieta M.
Villaverde, Antonio
Arís, Anna
Garcia-Fruitós, Elena
Ferrer-Miralles, Neus
Malouin, François
author_sort Carratalá, Jose V.
collection PubMed
description Oligomerization of antimicrobial peptides into nanosized supramolecular complexes produced in biological systems (inclusion bodies and self-assembling nanoparticles) seems an appealing alternative to conventional antibiotics. In this work, the antimicrobial peptide, GWH1, was N-terminally fused to two different scaffold proteins, namely, GFP and IFN-γ for its bacterial production in the form of such recombinant protein complexes. Protein self-assembling as regular soluble protein nanoparticles was achieved in the case of GWH1-GFP, while oligomerization into bacterial inclusion bodies was reached in both constructions. Among all these types of therapeutic proteins, protein nanoparticles of GWH1-GFP showed the highest bactericidal effect in an in vitro assay against Escherichia coli, whereas non-oligomerized GWH1-GFP and GWH1-IFN-γ only displayed a moderate bactericidal activity. These results indicate that the biological activity of GWH1 is specifically enhanced in the form of regular multi-display configurations. Those in vitro observations were fully validated against a bacterial infection using a mouse mastitis model, in which the GWH1-GFP soluble nanoparticles were able to effectively reduce bacterial loads.
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spelling pubmed-77664562020-12-28 In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics Carratalá, Jose V. Brouillette, Eric Serna, Naroa Sánchez-Chardi, Alejandro Sánchez, Julieta M. Villaverde, Antonio Arís, Anna Garcia-Fruitós, Elena Ferrer-Miralles, Neus Malouin, François Pharmaceutics Article Oligomerization of antimicrobial peptides into nanosized supramolecular complexes produced in biological systems (inclusion bodies and self-assembling nanoparticles) seems an appealing alternative to conventional antibiotics. In this work, the antimicrobial peptide, GWH1, was N-terminally fused to two different scaffold proteins, namely, GFP and IFN-γ for its bacterial production in the form of such recombinant protein complexes. Protein self-assembling as regular soluble protein nanoparticles was achieved in the case of GWH1-GFP, while oligomerization into bacterial inclusion bodies was reached in both constructions. Among all these types of therapeutic proteins, protein nanoparticles of GWH1-GFP showed the highest bactericidal effect in an in vitro assay against Escherichia coli, whereas non-oligomerized GWH1-GFP and GWH1-IFN-γ only displayed a moderate bactericidal activity. These results indicate that the biological activity of GWH1 is specifically enhanced in the form of regular multi-display configurations. Those in vitro observations were fully validated against a bacterial infection using a mouse mastitis model, in which the GWH1-GFP soluble nanoparticles were able to effectively reduce bacterial loads. MDPI 2020-12-17 /pmc/articles/PMC7766456/ /pubmed/33348529 http://dx.doi.org/10.3390/pharmaceutics12121217 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carratalá, Jose V.
Brouillette, Eric
Serna, Naroa
Sánchez-Chardi, Alejandro
Sánchez, Julieta M.
Villaverde, Antonio
Arís, Anna
Garcia-Fruitós, Elena
Ferrer-Miralles, Neus
Malouin, François
In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title_full In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title_fullStr In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title_full_unstemmed In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title_short In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
title_sort in vivo bactericidal efficacy of gwh1 antimicrobial peptide displayed on protein nanoparticles, a potential alternative to antibiotics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766456/
https://www.ncbi.nlm.nih.gov/pubmed/33348529
http://dx.doi.org/10.3390/pharmaceutics12121217
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