Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity

Abstract In the emerging era of antimicrobial resistance, the susceptibility to co-infections of patients suffering from either acquired or inherited hemolytic disorders can lead to dramatic increase in mortality rates. Closely related, heme liberated during hemolysis is one of the major sources of...

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Autores principales:	Tünde Juhász, Mayra Quemé-Peña, Bence Kővágó, Judith Mihály, Maria Ricci, Kata Horváti, Szilvia Bősze, Ferenc Zsila, Tamás Beke-Somfai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/303dc353fe50461882ecf5f2211cc1c0
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spelling	oai:doaj.org-article:303dc353fe50461882ecf5f2211cc1c02021-12-02T18:02:15ZInterplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity10.1038/s41598-021-97779-22045-2322https://doaj.org/article/303dc353fe50461882ecf5f2211cc1c02021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97779-2https://doaj.org/toc/2045-2322Abstract In the emerging era of antimicrobial resistance, the susceptibility to co-infections of patients suffering from either acquired or inherited hemolytic disorders can lead to dramatic increase in mortality rates. Closely related, heme liberated during hemolysis is one of the major sources of iron, which is vital for both host and invading microorganisms. While recent intensive research in the field has demonstrated that heme exerts diverse local effects including impairment of immune cells functions, it is almost completely unknown how it may compromise key molecules of our innate immune system, such as antimicrobial host defense peptides (HDPs). Since HDPs hold great promise as natural therapeutic agents against antibiotic-resistant microbes, understanding the effects that may modulate their action in microbial infection is crucial. Here we explore how hemin can interact directly with selected HDPs and influence their structure and membrane activity. It is revealed that induced helical folding, large assembly formation, and altered membrane activity is promoted by hemin. However, these effects showed variations depending mainly on peptide selectivity toward charged lipids, and the affinity of the peptide and hemin to lipid bilayers. Hemin-peptide complexes are sought to form semi-folded co-assemblies, which are present even with model membranes resembling mammalian or bacterial lipid compositions. In vitro cell-based toxicity assays supported that toxic effects of HDPs could be attenuated due to their assembly formation. These results are in line with our previous findings on peptide-lipid-small molecule systems suggesting that small molecules present in the complex in vivo milieu can regulate HDP function. Inversely, diverse effects of endogenous compounds could also be manipulated by HDPs.Tünde JuhászMayra Quemé-PeñaBence KővágóJudith MihályMaria RicciKata HorvátiSzilvia BőszeFerenc ZsilaTamás Beke-SomfaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tünde Juhász Mayra Quemé-Peña Bence Kővágó Judith Mihály Maria Ricci Kata Horváti Szilvia Bősze Ferenc Zsila Tamás Beke-Somfai Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
description	Abstract In the emerging era of antimicrobial resistance, the susceptibility to co-infections of patients suffering from either acquired or inherited hemolytic disorders can lead to dramatic increase in mortality rates. Closely related, heme liberated during hemolysis is one of the major sources of iron, which is vital for both host and invading microorganisms. While recent intensive research in the field has demonstrated that heme exerts diverse local effects including impairment of immune cells functions, it is almost completely unknown how it may compromise key molecules of our innate immune system, such as antimicrobial host defense peptides (HDPs). Since HDPs hold great promise as natural therapeutic agents against antibiotic-resistant microbes, understanding the effects that may modulate their action in microbial infection is crucial. Here we explore how hemin can interact directly with selected HDPs and influence their structure and membrane activity. It is revealed that induced helical folding, large assembly formation, and altered membrane activity is promoted by hemin. However, these effects showed variations depending mainly on peptide selectivity toward charged lipids, and the affinity of the peptide and hemin to lipid bilayers. Hemin-peptide complexes are sought to form semi-folded co-assemblies, which are present even with model membranes resembling mammalian or bacterial lipid compositions. In vitro cell-based toxicity assays supported that toxic effects of HDPs could be attenuated due to their assembly formation. These results are in line with our previous findings on peptide-lipid-small molecule systems suggesting that small molecules present in the complex in vivo milieu can regulate HDP function. Inversely, diverse effects of endogenous compounds could also be manipulated by HDPs.
format	article
author	Tünde Juhász Mayra Quemé-Peña Bence Kővágó Judith Mihály Maria Ricci Kata Horváti Szilvia Bősze Ferenc Zsila Tamás Beke-Somfai
author_facet	Tünde Juhász Mayra Quemé-Peña Bence Kővágó Judith Mihály Maria Ricci Kata Horváti Szilvia Bősze Ferenc Zsila Tamás Beke-Somfai
author_sort	Tünde Juhász
title	Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
title_short	Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
title_full	Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
title_fullStr	Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
title_full_unstemmed	Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
title_sort	interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/303dc353fe50461882ecf5f2211cc1c0
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Interplay between membrane active host defense peptides and heme modulates their assemblies and in vitro activity

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