Staphylococcus aureus Membrane-derived Vesicles Promote Bacterial Virulence and Confer Protective Immunity in Murine Infection Models

Abstract

<i>Staphylococcus aureus</i> produces membrane-derived vesicles (MVs), which share functional properties to outer membrane vesicles. Atomic force microscopy revealed that <i>S. aureus</i>-derived MVs are associated with the bacterial surface or released into the surrounding environment depending on bacterial growth conditions. By using a comparative proteomic approach, a total of 131 and 617 proteins were identified in MVs isolated from <i>S. aureus</i> grown in Luria-Bertani and brain-heart infusion broth, respectively. Purified <i>S. aureus</i> MVs derived from the bacteria grown in either media induced comparable levels of cytotoxicity and neutrophil-activation. Administration of exogenous MVs increased the resistance of <i>S. aureus</i> to killing by whole blood or purified human neutrophils ex vivo and increased <i>S. aureus</i> survival in vivo. Finally, immunization of mice with <i>S. aureus</i>-derived MVs induced production of IgM, total IgG, IgG1, IgG2a, and IgG2b resulting in protection against subcutaneous and systemic <i>S. aureus</i> infection. Collectively, our results suggest <i>S. aureus</i> MVs can influence bacterial–host interactions during systemic infections and provide protective immunity in murine models of infection.