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....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-94651-1 |
| _version_ | 1830082731963318272 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:06:13Z |
| format | Article |
| id | doaj.art-d79e59c52eb7439aaa4c53dd098bcdb8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T16:06:13Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d79e59c52eb7439aaa4c53dd098bcdb82022-12-21T22:55:05ZengNature PortfolioScientific Reports2045-23222021-07-0111111110.1038/s41598-021-94651-1High density lipoproteins mediate in vivo protection against staphylococcal phenol-soluble modulinsJosefien W. Hommes0Rachel M. Kratofil1Sigrid Wahlen2Carla J. C. de Haas3Reeni B. Hildebrand4G. Kees Hovingh5Micheal Otto6Miranda van Eck7Menno Hoekstra8Suzanne J. A. Korporaal9Bas G. J. Surewaard10Department of Microbiology, Immunology, and Infectious Disease. Snyder Institute for Chronic Diseases, University of CalgaryDepartment of Microbiology, Immunology, and Infectious Disease. Snyder Institute for Chronic Diseases, University of CalgaryMedical Microbiology, University Medical Center UtrechtMedical Microbiology, University Medical Center UtrechtDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus LaboratoriesDepartment of Vascular Medicine, Academic Medical CenterPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus LaboratoriesDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus LaboratoriesDivision of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus LaboratoriesDepartment of Microbiology, Immunology, and Infectious Disease. Snyder Institute for Chronic Diseases, University of CalgaryAbstract 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.https://doi.org/10.1038/s41598-021-94651-1 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-94651-1 |
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