Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus

Abstract Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cathrine Friberg, Jakob Krause Haaber, Martin Vestergaard, Anaëlle Fait, Veronique Perrot, Bruce R. Levin, Hanne Ingmer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba630a69cf7542e0b6becc235507cbc4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ba630a69cf7542e0b6becc235507cbc4
record_format	dspace
spelling	oai:doaj.org-article:ba630a69cf7542e0b6becc235507cbc42021-12-02T16:34:04ZHuman antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus10.1038/s41598-020-69962-42045-2322https://doaj.org/article/ba630a69cf7542e0b6becc235507cbc42020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-69962-4https://doaj.org/toc/2045-2322Abstract Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing a S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiological relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.Cathrine FribergJakob Krause HaaberMartin VestergaardAnaëlle FaitVeronique PerrotBruce R. LevinHanne IngmerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cathrine Friberg Jakob Krause Haaber Martin Vestergaard Anaëlle Fait Veronique Perrot Bruce R. Levin Hanne Ingmer Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
description	Abstract Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing a S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiological relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.
format	article
author	Cathrine Friberg Jakob Krause Haaber Martin Vestergaard Anaëlle Fait Veronique Perrot Bruce R. Levin Hanne Ingmer
author_facet	Cathrine Friberg Jakob Krause Haaber Martin Vestergaard Anaëlle Fait Veronique Perrot Bruce R. Levin Hanne Ingmer
author_sort	Cathrine Friberg
title	Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
title_short	Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
title_full	Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
title_fullStr	Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
title_full_unstemmed	Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
title_sort	human antimicrobial peptide, ll-37, induces non-inheritable reduced susceptibility to vancomycin in staphylococcus aureus
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/ba630a69cf7542e0b6becc235507cbc4
work_keys_str_mv	AT cathrinefriberg humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT jakobkrausehaaber humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT martinvestergaard humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT anaellefait humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT veroniqueperrot humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT brucerlevin humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus AT hanneingmer humanantimicrobialpeptidell37inducesnoninheritablereducedsusceptibilitytovancomycininstaphylococcusaureus
_version_	1718383777465499648

Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus

Ejemplares similares