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

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

Nature communications (2018-04-13)
Xiaogang Wang, Christopher D Thompson, Christopher Weidenmaier, Jean C Lee
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.

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Anti-Mouse IgG (Fc specific)–Alkaline Phosphatase antibody produced in goat, affinity isolated antibody, buffered aqueous solution