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Volume 12
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10.3390/pharmaceutics12121217
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Article

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

by
Jose V. Carratalá
1,2,3,
Eric Brouillette
4,5,
Naroa Serna
1,2,3,
Alejandro Sánchez-Chardi
6,7,
Julieta M. Sánchez
1,2,†,
Antonio Villaverde
1,2,3,
Anna Arís
8,
Elena Garcia-Fruitós
8,
Neus Ferrer-Miralles
1,2,3,* and
François Malouin
4,5,*
1
Institute for Biotechnology and Biomedicine, Autonomous University of Barcelona, Bellaterra, 08193 Barcelona, Spain
2
Department of Genetics and Microbiology, Autonomous University of Barcelona, Bellaterra, 08193 Barcelona, Spain
3
Bioengineering, Biomaterials and Nanomedicine Networking Biomedical Research Centre (CIBER-BBN), C/Monforte de Lemos 3-5, 28029 Madrid, Spain
4
Centre d’Étude et de Valorisation de la Diversité Microbienne (CEVDM), Département de Biologie, Université de Sherbrooke, 2500 Boul. Université, Sherbrooke, QC J1K 2R1, Canada
5
Mastitis Network and Regroupement de Recherche Pour un Lait de Qualité Optimale (Op+Lait), Université de Montréal, 2900 Edouard Montpetit Blvd, Montréal, QC H3T 1J4, Canada
6
Microscopy Service, Autonomous University of Barcelona, Bellaterra, 08193 Barcelona, Spain
7
Departament of Evolutionary Biology, Ecology and Environmental Sciences, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain
8
Department of Ruminant Production, Institute of Agriculture and Agrifood Research and Technology (IRTA), Caldes de Montbui, 08140 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
†
Permanent address: Faculty of Exact, Physical and Natural Sciences, ICTA and Chemistry Department, CONICET Institute of Biological and Technological Research (IIByT), National University of Cordoba, Velez Sarsfield Avenue 1611, X 5016GCA Córdoba, Argentina.
Pharmaceutics 2020, 12(12), 1217; https://doi.org/10.3390/pharmaceutics12121217
Received: 25 November 2020 / Revised: 11 December 2020 / Accepted: 14 December 2020 / Published: 17 December 2020
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Abstract

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. View Full-Text
Keywords: mouse mastitis model; antimicrobial peptide; protein nanoparticle; inclusion body; recombinant protein; Escherichia coli; Staphylococcus aureus; therapeutic protein mouse mastitis model; antimicrobial peptide; protein nanoparticle; inclusion body; recombinant protein; Escherichia coli; Staphylococcus aureus; therapeutic protein
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Carratalá, J.V.; Brouillette, E.; Serna, N.; Sánchez-Chardi, A.; Sánchez, J.M.; Villaverde, A.; Arís, A.; Garcia-Fruitós, E.; Ferrer-Miralles, N.; Malouin, F. In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics. Pharmaceutics 2020, 12, 1217. https://doi.org/10.3390/pharmaceutics12121217

AMA Style

Carratalá JV, Brouillette E, Serna N, Sánchez-Chardi A, Sánchez JM, Villaverde A, Arís A, Garcia-Fruitós E, Ferrer-Miralles N, Malouin F. In Vivo Bactericidal Efficacy of GWH1 Antimicrobial Peptide Displayed on Protein Nanoparticles, a Potential Alternative to Antibiotics. Pharmaceutics. 2020; 12(12):1217. https://doi.org/10.3390/pharmaceutics12121217

Chicago/Turabian Style

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, no. 12: 1217. https://doi.org/10.3390/pharmaceutics12121217

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