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

Abstract

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

Antibiotics Stimulate Formation of Vesicles in Staphylococcus aureus in both Phage-Dependent and -Independent Fashions and via Different Routes

“…The lower degree of protection we observed for MMC-induced CMVs than for FLU-induced CMVs in the bacterial protection assay could be due to the fact that CMVs induced by SOS response activation carry phage endolysins that can affect cell viability (4,25,26). Askarian et al recently showed that CMVs naturally produced by S. aureus protect cells from whole-blood killing (12). We observed a similar effect for CMVs produced by S. aureus in response to DNA damage or antibiotic stress, suggesting that the mechanism of CMV genesis does not affect the protective function of CMVs against the host innate immune defense (12).…”

“…Askarian et al recently showed that CMVs naturally produced by S. aureus protect cells from whole-blood killing (12). We observed a similar effect for CMVs produced by S. aureus in response to DNA damage or antibiotic stress, suggesting that the mechanism of CMV genesis does not affect the protective function of CMVs against the host innate immune defense (12). Since phage binding to the surface of strain CI1449 is impaired, the presence of phages in MMC-induced CMV preparations is not responsible for the protective effect observed against killing by DAP and whole blood.…”

“…The production of CMVs plays an important role in the delivery of S. aureus virulence factors to eukaryotic host cells (9,10), stimulates biofilm formation (11), increases resistance to killing by whole blood, and activates purified human neutrophils ex vivo. Mice immunized with CMVs were protected against subcutaneous and systemic S. aureus infections (12). CMVs were also shown to increase antibiotic resistance, since they can contain ␤-lactamases (13).…”

Proteome profiling of secreted and membrane vesicle associated proteins of an invasive and a commensal Staphylococcus haemolyticus isolate

“…Membrane vesicles (MVS) were isolated from a commensal S. haemolyticus strain (57-1), and a clinical S.haemolyticus strain (51-08), according to the methods described in [1], [4]. Briefly, proteins secreted into the bacterial growth medium was harvested after the culture was centrifuged and filtered through a 0.22 µm polyethersulfone membrane (Millipore express plus, Merck Millipore, Burlington, USA).…”

Vesicle-Mediated Dendritic Cell Activation in Acinetobacter baumannii Clinical Isolate, which Contributes to Th2 Response

“…OMVs can be considered having various roles in pathogenesis of bacteria, such as mediators of information exchange between bacteria and host [4] and vehicles of virulence factor transport [5]. Besides that, a recent study shows that bacterial OMVs have immunomodulatory activities, which make OMVs potential vaccine candidates for bacterial infection therapy and provide enlightened strategies for the development of antibacterial technologies [6][7][8]. Although there are amounts of evidences indicating that OMVs can trigger potent innate immune response in host cell and protect the host against bacterial infection [9,10], the exact mechanisms involved in the immune response induced by OMVs remain uncertain.…”