Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates

Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompati...

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Main Authors: Francisco G. Blanco, Roberto Vázquez, Ana M. Hernández-Arriaga, Pedro García, M. Auxiliadora Prieto
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2023.1220336/full
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author Francisco G. Blanco
Francisco G. Blanco
Roberto Vázquez
Ana M. Hernández-Arriaga
Ana M. Hernández-Arriaga
Pedro García
M. Auxiliadora Prieto
M. Auxiliadora Prieto
author_facet Francisco G. Blanco
Francisco G. Blanco
Roberto Vázquez
Ana M. Hernández-Arriaga
Ana M. Hernández-Arriaga
Pedro García
M. Auxiliadora Prieto
M. Auxiliadora Prieto
author_sort Francisco G. Blanco
collection DOAJ
description Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.
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spelling doaj.art-0d748cecd53342299ec34a74a3229b0e2023-06-28T09:04:24ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-06-011110.3389/fbioe.2023.12203361220336Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoatesFrancisco G. Blanco0Francisco G. Blanco1Roberto Vázquez2Ana M. Hernández-Arriaga3Ana M. Hernández-Arriaga4Pedro García5M. Auxiliadora Prieto6M. Auxiliadora Prieto7Polymer Biotechnology Group, Microbial and Plant Biotechnology Department, Margarita Salas Center for Biological Research (CIB–CSIC), Madrid, SpainInterdisciplinary Platform of Sustainable Plastics towards a Circular Economy, Spanish National Research Council (SusPlast-CSIC), Madrid, SpainProtein Engineering Against Antibiotic Resistance Group, Microbial and Plant Biotechnology Department, Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, SpainPolymer Biotechnology Group, Microbial and Plant Biotechnology Department, Margarita Salas Center for Biological Research (CIB–CSIC), Madrid, SpainInterdisciplinary Platform of Sustainable Plastics towards a Circular Economy, Spanish National Research Council (SusPlast-CSIC), Madrid, SpainProtein Engineering Against Antibiotic Resistance Group, Microbial and Plant Biotechnology Department, Margarita Salas Center for Biological Research (CIB-CSIC), Madrid, SpainPolymer Biotechnology Group, Microbial and Plant Biotechnology Department, Margarita Salas Center for Biological Research (CIB–CSIC), Madrid, SpainInterdisciplinary Platform of Sustainable Plastics towards a Circular Economy, Spanish National Research Council (SusPlast-CSIC), Madrid, SpainPolymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1220336/fullpolyhydroxyalkanoatesantimicrobial nanoparticlesantimicrobial materialsenzybioticsdrug delivery
spellingShingle Francisco G. Blanco
Francisco G. Blanco
Roberto Vázquez
Ana M. Hernández-Arriaga
Ana M. Hernández-Arriaga
Pedro García
M. Auxiliadora Prieto
M. Auxiliadora Prieto
Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
Frontiers in Bioengineering and Biotechnology
polyhydroxyalkanoates
antimicrobial nanoparticles
antimicrobial materials
enzybiotics
drug delivery
title Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
title_full Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
title_fullStr Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
title_full_unstemmed Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
title_short Enzybiotic-mediated antimicrobial functionalization of polyhydroxyalkanoates
title_sort enzybiotic mediated antimicrobial functionalization of polyhydroxyalkanoates
topic polyhydroxyalkanoates
antimicrobial nanoparticles
antimicrobial materials
enzybiotics
drug delivery
url https://www.frontiersin.org/articles/10.3389/fbioe.2023.1220336/full
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