In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics
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Autor/a
Carratalá, Jose V.
Brouillette, Eric
Serna, Naroa
Sánchez-Chardi, Alejandro
Sánchez, Julieta M.
Villaverde, Antonio
Arís, Anna
Ferrer-Miralles, Neus
Malouin, François
Fecha de publicación
2020-12-17ISSN
1999-4923
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
16
Publicado por
MDPI
Publicado en
Pharmaceutics
Citación
Carratalá, Jose V., Eric Brouillette, Naroa Serna, Alejandro Sánchez-Chardi, Julieta M. Sánchez, Antonio Villaverde, Anna Arís, Elena Garcia-Fruitós, Neus Ferrer-Miralles, and François Malouin. 2020. "In Vivo Bactericidal Efficacy Of GWH1 Antimicrobial Peptide Displayed On Protein Nanoparticles, A Potential Alternative To Antibiotics". Pharmaceutics 12 (12): 1217. doi:10.3390/pharmaceutics12121217.
Número del acuerdo de la subvención
MINECO/Programa Estatal de I+D+I orientada a los retos de la sociedad/RTA2015-00064-C02-02/ES/Validación del uso de las proteínas M-SAA3 y MMP-9 en la mejora del secado de la vaca de leche y optimización de su dosis efectiva mediante su nanoestructuración/
MINECO/Programa Estatal de I+D+I orientada a los retos de la sociedad/AGL2015-00064-C02-01/ES/Validación del uso de las proteínas M-SAA3 y MMP-9 en la mejora del secado de la vaca de leche y optimización de su dosis efectiva mediante su nanoestructuración/
Program
Producció de Remugants
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