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Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo

Antimicrobial resistance is an increasing threat to global health and challenges the way we treat infections. Peptides containing the PCNA interacting motif APIM (APIM-peptides) were recently shown to bind to the bacterial PCNA homolog, the beta (β)-clamp, and to have both antibacterial and anti-mut...

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Autores principales: Raeder, Synnøve Brandt, Sandbakken, Erik Thorvaldsen, Nepal, Anala, Løseth, Kirsti, Bergh, Kåre, Witsø, Eivind, Otterlei, Marit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009970/
https://www.ncbi.nlm.nih.gov/pubmed/33815313
http://dx.doi.org/10.3389/fmicb.2021.631557
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author Raeder, Synnøve Brandt
Sandbakken, Erik Thorvaldsen
Nepal, Anala
Løseth, Kirsti
Bergh, Kåre
Witsø, Eivind
Otterlei, Marit
author_facet Raeder, Synnøve Brandt
Sandbakken, Erik Thorvaldsen
Nepal, Anala
Løseth, Kirsti
Bergh, Kåre
Witsø, Eivind
Otterlei, Marit
author_sort Raeder, Synnøve Brandt
collection PubMed
description Antimicrobial resistance is an increasing threat to global health and challenges the way we treat infections. Peptides containing the PCNA interacting motif APIM (APIM-peptides) were recently shown to bind to the bacterial PCNA homolog, the beta (β)-clamp, and to have both antibacterial and anti-mutagenic activities. In this study we explore the antibacterial effects of these peptides on Staphylococcus epidermidis, a bacterial species commonly found in prosthetic joint infections (PJI). Drug-resistant bacterial isolates from PJIs often lead to difficult-to-treat chronic infections. We show that APIM-peptides have a rapid bactericidal effect which when used at sublethal levels also increase the efficacy of gentamicin. In addition, APIM-peptides reduce development and eliminate already existing S. epidermidis biofilm. To study the potential use of APIM-peptides to prevent PJI, we used an in vivo bone graft model in rats where APIM-peptide, gentamicin, or a combination of the two was added to cement. The bone grafts containing cement with the combination was more effective than cement containing only gentamicin, which is the current standard of care. In summary, these results suggest that APIM-peptides can be a promising new drug candidate for anti-infective implant materials to use in the fight against resistant bacteria and chronic PJI.
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spelling pubmed-80099702021-04-01 Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo Raeder, Synnøve Brandt Sandbakken, Erik Thorvaldsen Nepal, Anala Løseth, Kirsti Bergh, Kåre Witsø, Eivind Otterlei, Marit Front Microbiol Microbiology Antimicrobial resistance is an increasing threat to global health and challenges the way we treat infections. Peptides containing the PCNA interacting motif APIM (APIM-peptides) were recently shown to bind to the bacterial PCNA homolog, the beta (β)-clamp, and to have both antibacterial and anti-mutagenic activities. In this study we explore the antibacterial effects of these peptides on Staphylococcus epidermidis, a bacterial species commonly found in prosthetic joint infections (PJI). Drug-resistant bacterial isolates from PJIs often lead to difficult-to-treat chronic infections. We show that APIM-peptides have a rapid bactericidal effect which when used at sublethal levels also increase the efficacy of gentamicin. In addition, APIM-peptides reduce development and eliminate already existing S. epidermidis biofilm. To study the potential use of APIM-peptides to prevent PJI, we used an in vivo bone graft model in rats where APIM-peptide, gentamicin, or a combination of the two was added to cement. The bone grafts containing cement with the combination was more effective than cement containing only gentamicin, which is the current standard of care. In summary, these results suggest that APIM-peptides can be a promising new drug candidate for anti-infective implant materials to use in the fight against resistant bacteria and chronic PJI. Frontiers Media S.A. 2021-03-17 /pmc/articles/PMC8009970/ /pubmed/33815313 http://dx.doi.org/10.3389/fmicb.2021.631557 Text en Copyright © 2021 Raeder, Sandbakken, Nepal, Løseth, Bergh, Witsø and Otterlei. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Raeder, Synnøve Brandt
Sandbakken, Erik Thorvaldsen
Nepal, Anala
Løseth, Kirsti
Bergh, Kåre
Witsø, Eivind
Otterlei, Marit
Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title_full Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title_fullStr Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title_full_unstemmed Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title_short Novel Peptides Targeting the β-Clamp Rapidly Kill Planktonic and Biofilm Staphylococcus epidermidis Both in vitro and in vivo
title_sort novel peptides targeting the β-clamp rapidly kill planktonic and biofilm staphylococcus epidermidis both in vitro and in vivo
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009970/
https://www.ncbi.nlm.nih.gov/pubmed/33815313
http://dx.doi.org/10.3389/fmicb.2021.631557
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