AUTHOR=Askarian Fatemeh , Lapek John D. , Dongre Mitesh , Tsai Chih-Ming , Kumaraswamy Monika , Kousha Armin , Valderrama J. Andrés , Ludviksen Judith A. , Cavanagh Jorunn P. , Uchiyama Satoshi , Mollnes Tom E. , Gonzalez David J. , Wai Sun N. , Nizet Victor , Johannessen Mona 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00262

DOI=10.3389/fmicb.2018.00262

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic> produces membrane-derived vesicles (MVs), which share functional properties to outer membrane vesicles. Atomic force microscopy revealed that <italic>S. aureus</italic>-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 <italic>S. aureus</italic> grown in Luria-Bertani and brain-heart infusion broth, respectively. Purified <italic>S. aureus</italic> 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 <italic>S. aureus</italic> to killing by whole blood or purified human neutrophils <italic>ex vivo</italic> and increased <italic>S. aureus</italic> survival <italic>in vivo</italic>. Finally, immunization of mice with <italic>S. aureus</italic>-derived MVs induced production of IgM, total IgG, IgG1, IgG2a, and IgG2b resulting in protection against subcutaneous and systemic <italic>S. aureus</italic> infection. Collectively, our results suggest <italic>S. aureus</italic> MVs can influence bacterial–host interactions during systemic infections and provide protective immunity in murine models of infection.</p>