Wang, XiaogangThompson, ChristopherWeidenmaier, ChristopherLee, Jean2018-05-302018Wang, Xiaogang, Christopher D. Thompson, Christopher Weidenmaier, and Jean C. Lee. 2018. “Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform.” Nature Communications 9 (1): 1379. doi:10.1038/s41467-018-03847-z. http://dx.doi.org/10.1038/s41467-018-03847-z.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37067768Secretion 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.en-USJournal Article2018-05-3010.1038/s41467-018-03847-z