info:eu-repo/semantics/article
In vivo bactericidal efficacy of gwh1 antimicrobial peptide displayed on protein nanoparticles, a potential alternative to antibiotics
Fecha
2020-12Registro en:
Carratalá, Jose V.; Brouillette, Eric; Serna, Naroa; Sánchez-Chardi, Alejandro; Sanchez, Julieta Maria; et al.; In vivo bactericidal efficacy of gwh1 antimicrobial peptide displayed on protein nanoparticles, a potential alternative to antibiotics; MDPI AG; Pharmaceutics; 12; 12; 12-2020; 1-16
1999-4923
CONICET Digital
CONICET
Autor
Carratalá, Jose V.
Brouillette, Eric
Serna, Naroa
Sánchez-Chardi, Alejandro
Sanchez, Julieta Maria
Villaverde, Antonio
Arís, Anna
Garcia-Fruitós, Elena
Ferrer-Miralles, Neus
Malouin, François
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.