Title:
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In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
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Author:
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Carratalá, José Vicente; Brouillette, Eric; Serna, Naroa; Sánchez Chardi, Alejandro; Sanchez, Julieta M.; Villaverde Corrales, Antonio; Arís i Giralt, Anna; Garcia-Fruitos, Elena; Ferrer-Miralles, Neus; Malouin, François
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Abstract:
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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. |
Subject(s):
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-Mouse mastitis model -Antimicrobial peptide -Protein nanoparticle -Inclusion body -Recombinant protein -Escherichia coli -Staphylococcus aureus -Therapeutic protein |
Rights:
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open access
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https://creativecommons.org/licenses/by/4.0/ |
Document type:
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Article |
Published by:
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Share:
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Uri:
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https://ddd.uab.cat/record/236191
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