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

Xiaogang Wang, Christopher D. Thompson, Christopher Weidenmaier and Jean C. Lee ()
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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
Jean C. Lee: Brigham and Women’s Hospital and Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03847-z

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