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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7766456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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