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Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform

Author

Listed:
  • Xiaogang Wang

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Christopher D. Thompson

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Christopher Weidenmaier

    (University of Tuebingen
    Partner Site Tuebingen)

  • Jean C. Lee

    (Brigham and Women’s Hospital and Harvard Medical School)

Abstract

Secretion of extracellular vesicles (EVs), a process common to eukaryotes, archae, and bacteria, represents a secretory pathway that allows cell-free intercellular communication. Microbial EVs package diverse proteins and influence the host-pathogen interaction, but the mechanisms underlying EV production in Gram-positive bacteria are poorly understood. Here we show that EVs purified from community-associated methicillin-resistant Staphylococcus aureus package cytosolic, surface, and secreted proteins, including cytolysins. Staphylococcal alpha-type phenol-soluble modulins promote EV biogenesis by disrupting the cytoplasmic membrane; whereas, peptidoglycan cross-linking and autolysin activity modulate EV production by altering the permeability of the cell wall. We demonstrate that EVs purified from a S. aureus mutant that is genetically engineered to express detoxified cytolysins are immunogenic in mice, elicit cytolysin-neutralizing antibodies, and protect the animals in a lethal sepsis model. Our study reveals mechanisms underlying S. aureus EV production and highlights the usefulness of EVs as a S. aureus vaccine platform.

Suggested Citation

  • Xiaogang Wang & Christopher D. Thompson & Christopher Weidenmaier & Jean C. Lee, 2018. "Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03847-z
    DOI: 10.1038/s41467-018-03847-z
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    Cited by:

    1. Nele De Langhe & Sofie Van Dorpe & Niké Guilbert & Amélie Vander Cruyssen & Quentin Roux & Sarah Deville & Sándor Dedeyne & Philippe Tummers & Hannelore Denys & Linos Vandekerckhove & Olivier De Wever, 2024. "Mapping bacterial extracellular vesicle research: insights, best practices and knowledge gaps," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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