Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1783672971634671616 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8009970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT raedersynnøvebrandt novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT sandbakkenerikthorvaldsen novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT nepalanala novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT løsethkirsti novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT berghkare novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT witsøeivind novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo AT otterleimarit novelpeptidestargetingthebclamprapidlykillplanktonicandbiofilmstaphylococcusepidermidisbothinvitroandinvivo |