High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins

Abstract Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro....

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Autores principales:	Josefien W. Hommes, Rachel M. Kratofil, Sigrid Wahlen, Carla J. C. de Haas, Reeni B. Hildebrand, G. Kees Hovingh, Micheal Otto, Miranda van Eck, Menno Hoekstra, Suzanne J. A. Korporaal, Bas G. J. Surewaard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d79e59c52eb7439aaa4c53dd098bcdb8
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spelling	oai:doaj.org-article:d79e59c52eb7439aaa4c53dd098bcdb82021-12-02T16:31:48ZHigh density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins10.1038/s41598-021-94651-12045-2322https://doaj.org/article/d79e59c52eb7439aaa4c53dd098bcdb82021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94651-1https://doaj.org/toc/2045-2322Abstract Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.Josefien W. HommesRachel M. KratofilSigrid WahlenCarla J. C. de HaasReeni B. HildebrandG. Kees HovinghMicheal OttoMiranda van EckMenno HoekstraSuzanne J. A. KorporaalBas G. J. SurewaardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Josefien W. Hommes Rachel M. Kratofil Sigrid Wahlen Carla J. C. de Haas Reeni B. Hildebrand G. Kees Hovingh Micheal Otto Miranda van Eck Menno Hoekstra Suzanne J. A. Korporaal Bas G. J. Surewaard High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
description	Abstract Staphylococcus aureus virulence has been associated with the production of phenol-soluble modulins (PSMs). These PSMs have distinct virulence functions and are known to activate, attract and lyse neutrophils. These PSM-associated biological functions are inhibited by lipoproteins in vitro. We set out to address whether lipoproteins neutralize staphylococcal PSM-associated virulence in experimental animal models. Serum from both LCAT an ABCA1 knockout mice strains which are characterised by near absence of high-density lipoprotein (HDL) levels, was shown to fail to protect against PSM-induced neutrophil activation and lysis in vitro. Importantly, PSM-induced peritonitis in LCAT−/− mice resulted in increased lysis of resident peritoneal macrophages and enhanced neutrophil recruitment into the peritoneal cavity. Notably, LCAT−/− mice were more likely to succumb to staphylococcal bloodstream infections in a PSM-dependent manner. Plasma from homozygous carriers of ABCA1 variants characterized by very low HDL-cholesterol levels, was found to be less protective against PSM-mediated biological functions compared to healthy humans. Therefore, we conclude that lipoproteins present in blood can protect against staphylococcal PSMs, the key virulence factor of community-associated methicillin resistant S. aureus.
format	article
author	Josefien W. Hommes Rachel M. Kratofil Sigrid Wahlen Carla J. C. de Haas Reeni B. Hildebrand G. Kees Hovingh Micheal Otto Miranda van Eck Menno Hoekstra Suzanne J. A. Korporaal Bas G. J. Surewaard
author_facet	Josefien W. Hommes Rachel M. Kratofil Sigrid Wahlen Carla J. C. de Haas Reeni B. Hildebrand G. Kees Hovingh Micheal Otto Miranda van Eck Menno Hoekstra Suzanne J. A. Korporaal Bas G. J. Surewaard
author_sort	Josefien W. Hommes
title	High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
title_short	High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
title_full	High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
title_fullStr	High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
title_full_unstemmed	High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
title_sort	high density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d79e59c52eb7439aaa4c53dd098bcdb8
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High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulins

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