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...

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Autores principales:	Anala Nepal, Synnøve Brandt Ræder, Caroline Krogh Søgaard, Maria Schei Haugan, Marit Otterlei
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	APIM antimicrobial resistance β-clamp translesion synthesis antibacterial peptide antimutagenic Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/550a1bbe79fe423aaec59f6b24cd16eb
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spelling	oai:doaj.org-article:550a1bbe79fe423aaec59f6b24cd16eb2021-12-01T05:59:05ZBroad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization1664-302X10.3389/fmicb.2021.764451https://doaj.org/article/550a1bbe79fe423aaec59f6b24cd16eb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.764451/fullhttps://doaj.org/toc/1664-302XNew 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.Anala NepalSynnøve Brandt RæderCaroline Krogh SøgaardMaria Schei HauganMarit OtterleiMarit OtterleiFrontiers Media S.A.articleAPIMantimicrobial resistanceβ-clamptranslesion synthesisantibacterial peptideantimutagenicMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	APIM antimicrobial resistance β-clamp translesion synthesis antibacterial peptide antimutagenic Microbiology QR1-502
spellingShingle	APIM antimicrobial resistance β-clamp translesion synthesis antibacterial peptide antimutagenic Microbiology QR1-502 Anala Nepal Synnøve Brandt Ræder Caroline Krogh Søgaard Maria Schei Haugan Marit Otterlei Marit Otterlei Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization
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	article
author	Anala Nepal Synnøve Brandt Ræder Caroline Krogh Søgaard Maria Schei Haugan Marit Otterlei Marit Otterlei
author_facet	Anala Nepal Synnøve Brandt Ræder Caroline Krogh Søgaard Maria Schei Haugan Marit Otterlei Marit Otterlei
author_sort	Anala Nepal
title	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_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_sort	broad-spectrum antibacterial peptide kills extracellular and intracellular bacteria without affecting epithelialization
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/550a1bbe79fe423aaec59f6b24cd16eb
work_keys_str_mv	AT analanepal broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization AT synnøvebrandtræder broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization AT carolinekroghsøgaard broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization AT mariascheihaugan broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization AT maritotterlei broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization AT maritotterlei broadspectrumantibacterialpeptidekillsextracellularandintracellularbacteriawithoutaffectingepithelialization
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Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization

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