Acinetobacter nosocomialis secretes outer membrane vesicles that induce epithelial cell death and host inflammatory responses

Acinetobacter nosocomialis is an important nosocomial pathogen that causes a variety of opportunistic infections; however, pathogenesis of this microorganism has not yet been characterized. The aim of this study was to investigate the secretion of outer membrane vesicles (OMVs) from A.nosocomialis and to determine their cytotoxic effects and their ability to induce inflammatory responses both invitro and invivo by using human epithelial HEp-2 cells and a mouse model, respectively. A.nosocomialis ATCC 17903^T secreted spherical OMVs when cultured invitro. Proteomic analysis revealed that 147 different proteins were associated with A.nosocomialis OMVs and virulence-associated proteins, such as outer membrane protein A (OmpA), CsuA, CsuC, CsuD, PilW, hemolysin, and serine protease, were identified. A.nosocomialis OMVs were cytotoxic to HEp-2 cells. These vesicles also induced the expression of pro-inflammatory cytokine genes in the HEp-2 cells. Early inflammatory responses, such as congestion and focal neutrophilic infiltration, were observed in the lungs of mice injected with A.nosocomialis OMVs. In conclusion, A.nosocomialis OMVs are important secretory nanocomplexes that induce cytotoxicity of epithelial cells and host inflammatory responses, which may contribute to the pathogenesis of A.nosocomialis.