Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm

In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibili...

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Autores principales:	Francesca Berini, Viviana Teresa Orlandi, Federica Gamberoni, Eleonora Martegani, Ilaria Armenia, Rosalba Gornati, Giovanni Bernardini, Flavia Marinelli
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	magnetic nanoparticles iron oxide nanoparticles teicoplanin vancomycin antimicrobial resistance biofilm Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/53b0057774b54819b9a35a648d52a716
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spelling	oai:doaj.org-article:53b0057774b54819b9a35a648d52a7162021-12-02T10:05:59ZAntimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm1664-302X10.3389/fmicb.2021.657431https://doaj.org/article/53b0057774b54819b9a35a648d52a7162021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.657431/fullhttps://doaj.org/toc/1664-302XIn the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation. As a consequence of antibiotic localization, a decrease in its administration dosage might be possible, reducing the side effects to non-targeted organs and the risk of antibiotic resistance spread in the commensal microbiota. Here, we prepared nanoformulations of the ‘last-resort’ glycopeptides teicoplanin and vancomycin by conjugating them to IONPs via surface functionalization with (3-aminopropyl) triethoxysilane (APTES). These superparamagnetic NP-TEICO and NP-VANCO were chemically stable and NP-TEICO (better than NP-VANCO) conserved the typical spectrum of antimicrobial activity of glycopeptide antibiotics, being effective against a panel of staphylococci and enterococci, including clinical isolates and resistant strains. By a combination of different methodological approaches, we proved that NP-TEICO and, although to a lesser extent, NP-VANCO were effective in reducing biofilm formation by three methicillin-sensitive or resistant Staphylococcus aureus strains. Moreover, when attracted and concentrated by the action of an external magnet, NP-TEICO exerted a localized inhibitory effect on S. aureus biofilm formation at low antibiotic concentration. Finally, we proved that the conjugation of glycopeptide antibiotics to IONPs reduced their intrinsic cytotoxicity toward a human cell line.Francesca BeriniViviana Teresa OrlandiFederica GamberoniEleonora MarteganiIlaria ArmeniaRosalba GornatiGiovanni BernardiniFlavia MarinelliFrontiers Media S.A.articlemagnetic nanoparticlesiron oxide nanoparticlesteicoplaninvancomycinantimicrobial resistancebiofilmMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	magnetic nanoparticles iron oxide nanoparticles teicoplanin vancomycin antimicrobial resistance biofilm Microbiology QR1-502
spellingShingle	magnetic nanoparticles iron oxide nanoparticles teicoplanin vancomycin antimicrobial resistance biofilm Microbiology QR1-502 Francesca Berini Viviana Teresa Orlandi Federica Gamberoni Eleonora Martegani Ilaria Armenia Rosalba Gornati Giovanni Bernardini Flavia Marinelli Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
description	In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation. As a consequence of antibiotic localization, a decrease in its administration dosage might be possible, reducing the side effects to non-targeted organs and the risk of antibiotic resistance spread in the commensal microbiota. Here, we prepared nanoformulations of the ‘last-resort’ glycopeptides teicoplanin and vancomycin by conjugating them to IONPs via surface functionalization with (3-aminopropyl) triethoxysilane (APTES). These superparamagnetic NP-TEICO and NP-VANCO were chemically stable and NP-TEICO (better than NP-VANCO) conserved the typical spectrum of antimicrobial activity of glycopeptide antibiotics, being effective against a panel of staphylococci and enterococci, including clinical isolates and resistant strains. By a combination of different methodological approaches, we proved that NP-TEICO and, although to a lesser extent, NP-VANCO were effective in reducing biofilm formation by three methicillin-sensitive or resistant Staphylococcus aureus strains. Moreover, when attracted and concentrated by the action of an external magnet, NP-TEICO exerted a localized inhibitory effect on S. aureus biofilm formation at low antibiotic concentration. Finally, we proved that the conjugation of glycopeptide antibiotics to IONPs reduced their intrinsic cytotoxicity toward a human cell line.
format	article
author	Francesca Berini Viviana Teresa Orlandi Federica Gamberoni Eleonora Martegani Ilaria Armenia Rosalba Gornati Giovanni Bernardini Flavia Marinelli
author_facet	Francesca Berini Viviana Teresa Orlandi Federica Gamberoni Eleonora Martegani Ilaria Armenia Rosalba Gornati Giovanni Bernardini Flavia Marinelli
author_sort	Francesca Berini
title	Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
title_short	Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
title_full	Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
title_fullStr	Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
title_full_unstemmed	Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm
title_sort	antimicrobial activity of nanoconjugated glycopeptide antibiotics and their effect on staphylococcus aureus biofilm
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/53b0057774b54819b9a35a648d52a716
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Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm

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