Cargando…

Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization

New antibacterial drugs with novel modes of action are urgently needed as antibiotic resistance in bacteria is increasing and spreading throughout the world. In this study, we aimed to explore the possibility of using APIM-peptides targeting the bacterial β-clamp for treatment of skin infections. We...

Descripción completa

Detalles Bibliográficos
Autores principales: Nepal, Anala, Ræder, Synnøve Brandt, Søgaard, Caroline Krogh, Haugan, Maria Schei, 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/PMC8661032/
https://www.ncbi.nlm.nih.gov/pubmed/34899646
http://dx.doi.org/10.3389/fmicb.2021.764451
_version_ 1784613310270799872
author Nepal, Anala
Ræder, Synnøve Brandt
Søgaard, Caroline Krogh
Haugan, Maria Schei
Otterlei, Marit
author_facet Nepal, Anala
Ræder, Synnøve Brandt
Søgaard, Caroline Krogh
Haugan, Maria Schei
Otterlei, Marit
author_sort Nepal, Anala
collection PubMed
description New antibacterial drugs with novel modes of action are urgently needed as antibiotic resistance in bacteria is increasing and spreading throughout the world. In this study, we aimed to explore the possibility of using APIM-peptides targeting the bacterial β-clamp for treatment of skin infections. We selected a lead peptide, named betatide, from five APIM-peptide candidates based on their antibacterial and antimutagenic activities in both G(+) and G(–) bacteria. Betatide was further tested in minimal inhibitory concentration (MIC) assays in ESKAPE pathogens, in in vitro infection models, and in a resistance development assay. We found that betatide is a broad-range antibacterial which obliterated extracellular bacterial growth of methicillin-resistant Staphylococcus epidermidis (MRSE) in cell co-cultures without affecting the epithelialization of HaCaT keratinocytes. Betatide also reduced the number of intracellular Staphylococcus aureus in infected HaCaT cells. Furthermore, long-time exposure to betatide at sub-MICs induced minimal or no increase in resistance development compared to ciprofloxacin and gentamicin or ampicillin in S. aureus and Escherichia coli. These properties support the potential of betatide for the treatment of topical skin infections.
format Online
Article
Text
id pubmed-8661032
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86610322021-12-11 Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization Nepal, Anala Ræder, Synnøve Brandt Søgaard, Caroline Krogh Haugan, Maria Schei Otterlei, Marit Front Microbiol Microbiology New antibacterial drugs with novel modes of action are urgently needed as antibiotic resistance in bacteria is increasing and spreading throughout the world. In this study, we aimed to explore the possibility of using APIM-peptides targeting the bacterial β-clamp for treatment of skin infections. We selected a lead peptide, named betatide, from five APIM-peptide candidates based on their antibacterial and antimutagenic activities in both G(+) and G(–) bacteria. Betatide was further tested in minimal inhibitory concentration (MIC) assays in ESKAPE pathogens, in in vitro infection models, and in a resistance development assay. We found that betatide is a broad-range antibacterial which obliterated extracellular bacterial growth of methicillin-resistant Staphylococcus epidermidis (MRSE) in cell co-cultures without affecting the epithelialization of HaCaT keratinocytes. Betatide also reduced the number of intracellular Staphylococcus aureus in infected HaCaT cells. Furthermore, long-time exposure to betatide at sub-MICs induced minimal or no increase in resistance development compared to ciprofloxacin and gentamicin or ampicillin in S. aureus and Escherichia coli. These properties support the potential of betatide for the treatment of topical skin infections. Frontiers Media S.A. 2021-11-26 /pmc/articles/PMC8661032/ /pubmed/34899646 http://dx.doi.org/10.3389/fmicb.2021.764451 Text en Copyright © 2021 Nepal, Ræder, Søgaard, Haugan and Otterlei. https://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
Nepal, Anala
Ræder, Synnøve Brandt
Søgaard, Caroline Krogh
Haugan, Maria Schei
Otterlei, Marit
Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title_full Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title_fullStr Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title_full_unstemmed Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title_short Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
title_sort broad-spectrum antibacterial peptide kills extracellular and intracellular bacteria without affecting epithelialization
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661032/
https://www.ncbi.nlm.nih.gov/pubmed/34899646
http://dx.doi.org/10.3389/fmicb.2021.764451
work_keys_str_mv AT nepalanala broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization
AT rædersynnøvebrandt broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization
AT søgaardcarolinekrogh broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization
AT hauganmariaschei broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization
AT otterleimarit broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization