title: Acinetobacter nosocomialis secretes outer membrane vesicles that induce epithelial cell death and host inflammatory responses.
abstract: 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 in vitro and in vivo by using human epithelial HEp-2 cells and a mouse model, respectively. A. nosocomialis ATCC 17903(T) secreted spherical OMVs when cultured in vitro. 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.
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jae Su
authors.initials: JS
authors.lastname: Nho
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Jun
authors.affiliation: Department of Nanobiomedical Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Man Hwan
authors.initials: MH
authors.lastname: Oh
authors.affiliation: Department of Pathology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Tai In
authors.initials: TI
authors.lastname: Park
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea.
authors.forename: Chi Won
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea.
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Chul Hee
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea. Electronic address: leejc@knu.ac.kr.
authors.forename: Je Chul
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000150:Acinetobacter / Q000276:immunology* / Q000378:metabolism*; D000151:Acinetobacter Infections / Q000276:immunology / Q000473:pathology; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D016923:Cell Death; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000473:pathology; D051379:Mice; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism*; D037521:Virulence Factors / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors
keywords: Cytokine; Cytotoxicity; Nosocomial pathogen; Pathogenesis; Virulence factor