Pharmaceutics (Dec 2020)

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

  • Jose V. Carratalá,
  • Eric Brouillette,
  • Naroa Serna,
  • Alejandro Sánchez-Chardi,
  • Julieta M. Sánchez,
  • Antonio Villaverde,
  • Anna Arís,
  • Elena Garcia-Fruitós,
  • Neus Ferrer-Miralles,
  • François Malouin

DOI
https://doi.org/10.3390/pharmaceutics12121217
Journal volume & issue
Vol. 12, no. 12
p. 1217

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.

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