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 Acinetobacter nosocomialis and to determine their cytotoxic effects and their ability to induce inflammatory responses both in vitro and in vivo by using human epithelial HEp-2 cells and a mouse model, respectively. Acinetobacter nosocomialis ATCC 17903(T) secreted spherical OMVs when cultured in vitro. Proteomic analysis revealed that 147 different proteins were associated with Acinetobacter nosocomialis OMVs and virulence-associated proteins, such as outer membrane protein A (OmpA), CsuA, CsuC, CsuD, PilW, hemolysin, and serine protease, were identified. Acinetobacter nosocomialis OMVs were cytotoxic to HEp-2 cells. These vesicles also induced the expression of proinflammatory 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 Acinetobacter nosocomialis OMVs. In conclusion, Acinetobacter nosocomialis OMVs are important secretory nanocomplexes that induce cytotoxicity of epithelial cells and host inflammatory responses, which may contribute to the pathogenesis of Acinetobacter nosocomialis. (C) 2015 Elsevier Ltd. All rights reserved.