BOB体育

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Title Molecular Pathogenesis of Acinetobacter baumannii: The Role of Outer Membrane Protein A

Presented by Je Chul Lee, M.D., Ph.D. Professor and Chair Department of Microbiology School of Medicine Kyungpook National University Daegu, Korea

Acinetobacter baumannii is an important opportunistic pathogen that causes a variety of human infections. Despite the considerable clinical data regarding the role of A. baumannii in nosocomial infection, pathogenic mechanisms of this organism have yet to be fully understood. Our group demonstrated that a major envelope protein, outer membrane protein A (AbOmpA), is a potential virulence factor of A. baumannii. AbOmpA is secreted from A. baumannii via outer membrane vesicles (OMVs), which enter host cells through a cholesterol-rich membrane microdomain. AbOmpA is targeted to both mitochondria and nuclei. AbOmpA is interacted with voltage-dependent anion channel on the outer membrane of mitochondria, followed by the elevation of mitochondrial transmembrane potential and an increase of intracellular ROS. These events induce mitochondrial swelling, caspase activation, and apoptosis of host cells. In addition, AbOmpA targets in the nuclei of host cells by a monopartite nuclear localization signal. The nuclear AbOmpA induces host cell death through DNase l-like activity. A bacteria-bound AbOmpA is responsible for adherence to and invasion of bacteria in epithelial cells and inhibits the complement-mediated lysis of bacteria, whereas the secreted AbOmpA via OMVs plays a role in disintegration of mucosal lining and immunopathology of A. baumannii infection.