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Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus

Staphylococcus aureus is a pathogenic bacterium but also a commensal of skin and anterior nares in humans. As S. aureus transits from skins/nares to inside the human body, it experiences changes in temperature. The production and content of S. aureus extracellular vesicles (EVs) have been increasing...

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Autores principales: Briaud, Paul, Frey, Andrew, Marino, Emily C., Bastock, Raeven A., Zielinski, Riley E., Wiemels, Richard E., Keogh, Rebecca A., Murphy, Erin R., Shaw, Lindsey N., Carroll, Ronan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510519/
https://www.ncbi.nlm.nih.gov/pubmed/34612674
http://dx.doi.org/10.1128/mSphere.00676-21
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author Briaud, Paul
Frey, Andrew
Marino, Emily C.
Bastock, Raeven A.
Zielinski, Riley E.
Wiemels, Richard E.
Keogh, Rebecca A.
Murphy, Erin R.
Shaw, Lindsey N.
Carroll, Ronan K.
author_facet Briaud, Paul
Frey, Andrew
Marino, Emily C.
Bastock, Raeven A.
Zielinski, Riley E.
Wiemels, Richard E.
Keogh, Rebecca A.
Murphy, Erin R.
Shaw, Lindsey N.
Carroll, Ronan K.
author_sort Briaud, Paul
collection PubMed
description Staphylococcus aureus is a pathogenic bacterium but also a commensal of skin and anterior nares in humans. As S. aureus transits from skins/nares to inside the human body, it experiences changes in temperature. The production and content of S. aureus extracellular vesicles (EVs) have been increasingly studied over the past few years, and EVs are increasingly being recognized as important to the infectious process. Nonetheless, the impact of temperature variation on S. aureus EVs has not been studied in detail, as most reports that investigate EV cargoes and host cell interactions are performed using vesicles produced at 37°C. Here, we report that EVs in S. aureus differ in size and protein/RNA cargo depending on the growth temperature used. We demonstrate that the temperature-dependent regulation of vesicle production in S. aureus is mediated by the alpha phenol-soluble modulin peptides (αPSMs). Through proteomic analysis, we observed increased packaging of virulence factors at 40°C, whereas the EV proteome has greater diversity at 34°C. Similar to the protein content, we perform transcriptomic analysis and demonstrate that the RNA cargo also is impacted by temperature. Finally, we demonstrate greater αPSM- and alpha-toxin-mediated erythrocyte lysis with 40°C EVs, but 34°C EVs are more cytotoxic toward THP-1 cells. Together, our study demonstrates that small temperature variations have great impact on EV biogenesis and shape the interaction with host cells. IMPORTANCE Extracellular vesicles (EVs) are lipid bilayer spheres that contain proteins, nucleic acids, and lipids secreted by bacteria. They are involved in Staphylococcus aureus infections, as they package virulence factors and deliver their contents inside host cells. The impact of temperature variations experienced by S. aureus during the infectious process on EVs is unknown. Here, we demonstrate the importance of temperature in vesicle production and packaging. High temperatures promote packaging of virulence factors and increase the protein and lipid concentration but reduce the overall RNA abundance and protein diversity in EVs. The importance of temperature changes is highlighted by the fact that EVs produced at low temperature are more toxic toward macrophages, whereas EVs produced at high temperature display more hemolysis toward erythrocytes. Our research brings new insights into temperature-dependent vesiculation and interaction with the host during S. aureus transition from colonization to virulence.
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spelling pubmed-85105192021-11-04 Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus Briaud, Paul Frey, Andrew Marino, Emily C. Bastock, Raeven A. Zielinski, Riley E. Wiemels, Richard E. Keogh, Rebecca A. Murphy, Erin R. Shaw, Lindsey N. Carroll, Ronan K. mSphere Research Article Staphylococcus aureus is a pathogenic bacterium but also a commensal of skin and anterior nares in humans. As S. aureus transits from skins/nares to inside the human body, it experiences changes in temperature. The production and content of S. aureus extracellular vesicles (EVs) have been increasingly studied over the past few years, and EVs are increasingly being recognized as important to the infectious process. Nonetheless, the impact of temperature variation on S. aureus EVs has not been studied in detail, as most reports that investigate EV cargoes and host cell interactions are performed using vesicles produced at 37°C. Here, we report that EVs in S. aureus differ in size and protein/RNA cargo depending on the growth temperature used. We demonstrate that the temperature-dependent regulation of vesicle production in S. aureus is mediated by the alpha phenol-soluble modulin peptides (αPSMs). Through proteomic analysis, we observed increased packaging of virulence factors at 40°C, whereas the EV proteome has greater diversity at 34°C. Similar to the protein content, we perform transcriptomic analysis and demonstrate that the RNA cargo also is impacted by temperature. Finally, we demonstrate greater αPSM- and alpha-toxin-mediated erythrocyte lysis with 40°C EVs, but 34°C EVs are more cytotoxic toward THP-1 cells. Together, our study demonstrates that small temperature variations have great impact on EV biogenesis and shape the interaction with host cells. IMPORTANCE Extracellular vesicles (EVs) are lipid bilayer spheres that contain proteins, nucleic acids, and lipids secreted by bacteria. They are involved in Staphylococcus aureus infections, as they package virulence factors and deliver their contents inside host cells. The impact of temperature variations experienced by S. aureus during the infectious process on EVs is unknown. Here, we demonstrate the importance of temperature in vesicle production and packaging. High temperatures promote packaging of virulence factors and increase the protein and lipid concentration but reduce the overall RNA abundance and protein diversity in EVs. The importance of temperature changes is highlighted by the fact that EVs produced at low temperature are more toxic toward macrophages, whereas EVs produced at high temperature display more hemolysis toward erythrocytes. Our research brings new insights into temperature-dependent vesiculation and interaction with the host during S. aureus transition from colonization to virulence. American Society for Microbiology 2021-10-06 /pmc/articles/PMC8510519/ /pubmed/34612674 http://dx.doi.org/10.1128/mSphere.00676-21 Text en Copyright © 2021 Briaud et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Briaud, Paul
Frey, Andrew
Marino, Emily C.
Bastock, Raeven A.
Zielinski, Riley E.
Wiemels, Richard E.
Keogh, Rebecca A.
Murphy, Erin R.
Shaw, Lindsey N.
Carroll, Ronan K.
Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title_full Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title_fullStr Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title_full_unstemmed Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title_short Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus
title_sort temperature influences the composition and cytotoxicity of extracellular vesicles in staphylococcus aureus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510519/
https://www.ncbi.nlm.nih.gov/pubmed/34612674
http://dx.doi.org/10.1128/mSphere.00676-21
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