The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT The innate immune system uses Toll-like receptor (TLR) 2 to detect conserved bacterial lipoproteins of invading pathogens. The lipid anchor attaches lipoproteins to the cytoplasmic membrane and prevents their release from the bacterial cell envelope. How bacteria release lipoproteins and ho...

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Autores principales:	Katja Schlatterer, Christian Beck, Dennis Hanzelmann, Marco Lebtig, Birgit Fehrenbacher, Martin Schaller, Patrick Ebner, Mulugeta Nega, Michael Otto, Dorothee Kretschmer, Andreas Peschel
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Staphylococcus aureus leukocytes lipoproteins pore-forming toxins Toll-like receptors vesicles Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/50db06f6b2f1472d8fdc42ff1add844b
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spelling	oai:doaj.org-article:50db06f6b2f1472d8fdc42ff1add844b2021-11-15T15:52:19ZThe Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.01851-182150-7511https://doaj.org/article/50db06f6b2f1472d8fdc42ff1add844b2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01851-18https://doaj.org/toc/2150-7511ABSTRACT The innate immune system uses Toll-like receptor (TLR) 2 to detect conserved bacterial lipoproteins of invading pathogens. The lipid anchor attaches lipoproteins to the cytoplasmic membrane and prevents their release from the bacterial cell envelope. How bacteria release lipoproteins and how these molecules reach TLR2 remain unknown. Staphylococcus aureus has been described to liberate membrane vesicles. The composition, mode of release, and relevance for microbe-host interaction of such membrane vesicles have remained ambiguous. We recently reported that S. aureus can release lipoproteins only when surfactant-like small peptides, the phenol-soluble modulins (PSMs), are expressed. Here we demonstrate that PSM peptides promote the release of membrane vesicles from the cytoplasmic membrane of S. aureus via an increase in membrane fluidity, and we provide evidence that the bacterial turgor is the driving force for vesicle budding under hypotonic osmotic conditions. Intriguingly, the majority of lipoproteins are released by S. aureus as components of membrane vesicles, and this process depends on surfactant-like molecules such as PSMs. Vesicle disruption at high detergent concentrations promotes the capacity of lipoproteins to activate TLR2. These results reveal that vesicle release by bacterium-derived surfactants is required for TLR2-mediated inflammation. IMPORTANCE Our study highlights the roles of surfactant-like molecules in bacterial inflammation with important implications for the prevention and therapy of inflammatory disorders. It describes a potential pathway for the transfer of hydrophobic bacterial lipoproteins, the major TLR2 agonists, from the cytoplasmic membrane of Gram-positive bacteria to the TLR2 receptor at the surface of host cells. Moreover, our study reveals a molecular mechanism that explains how cytoplasmic and membrane-embedded bacterial proteins can be released by bacterial cells without using any of the typical protein secretion routes, thereby contributing to our understanding of the processes used by bacteria to communicate with host organisms and the environment.Katja SchlattererChristian BeckDennis HanzelmannMarco LebtigBirgit FehrenbacherMartin SchallerPatrick EbnerMulugeta NegaMichael OttoDorothee KretschmerAndreas PeschelAmerican Society for MicrobiologyarticleStaphylococcus aureusleukocyteslipoproteinspore-forming toxinsToll-like receptorsvesiclesMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus leukocytes lipoproteins pore-forming toxins Toll-like receptors vesicles Microbiology QR1-502
spellingShingle	Staphylococcus aureus leukocytes lipoproteins pore-forming toxins Toll-like receptors vesicles Microbiology QR1-502 Katja Schlatterer Christian Beck Dennis Hanzelmann Marco Lebtig Birgit Fehrenbacher Martin Schaller Patrick Ebner Mulugeta Nega Michael Otto Dorothee Kretschmer Andreas Peschel The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT The innate immune system uses Toll-like receptor (TLR) 2 to detect conserved bacterial lipoproteins of invading pathogens. The lipid anchor attaches lipoproteins to the cytoplasmic membrane and prevents their release from the bacterial cell envelope. How bacteria release lipoproteins and how these molecules reach TLR2 remain unknown. Staphylococcus aureus has been described to liberate membrane vesicles. The composition, mode of release, and relevance for microbe-host interaction of such membrane vesicles have remained ambiguous. We recently reported that S. aureus can release lipoproteins only when surfactant-like small peptides, the phenol-soluble modulins (PSMs), are expressed. Here we demonstrate that PSM peptides promote the release of membrane vesicles from the cytoplasmic membrane of S. aureus via an increase in membrane fluidity, and we provide evidence that the bacterial turgor is the driving force for vesicle budding under hypotonic osmotic conditions. Intriguingly, the majority of lipoproteins are released by S. aureus as components of membrane vesicles, and this process depends on surfactant-like molecules such as PSMs. Vesicle disruption at high detergent concentrations promotes the capacity of lipoproteins to activate TLR2. These results reveal that vesicle release by bacterium-derived surfactants is required for TLR2-mediated inflammation. IMPORTANCE Our study highlights the roles of surfactant-like molecules in bacterial inflammation with important implications for the prevention and therapy of inflammatory disorders. It describes a potential pathway for the transfer of hydrophobic bacterial lipoproteins, the major TLR2 agonists, from the cytoplasmic membrane of Gram-positive bacteria to the TLR2 receptor at the surface of host cells. Moreover, our study reveals a molecular mechanism that explains how cytoplasmic and membrane-embedded bacterial proteins can be released by bacterial cells without using any of the typical protein secretion routes, thereby contributing to our understanding of the processes used by bacteria to communicate with host organisms and the environment.
format	article
author	Katja Schlatterer Christian Beck Dennis Hanzelmann Marco Lebtig Birgit Fehrenbacher Martin Schaller Patrick Ebner Mulugeta Nega Michael Otto Dorothee Kretschmer Andreas Peschel
author_facet	Katja Schlatterer Christian Beck Dennis Hanzelmann Marco Lebtig Birgit Fehrenbacher Martin Schaller Patrick Ebner Mulugeta Nega Michael Otto Dorothee Kretschmer Andreas Peschel
author_sort	Katja Schlatterer
title	The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	mechanism behind bacterial lipoprotein release: phenol-soluble modulins mediate toll-like receptor 2 activation via extracellular vesicle release from <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/50db06f6b2f1472d8fdc42ff1add844b
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The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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