acinetobacter baumannii secretes cytotoxic outer membrane protein a via outer membrane vesicles鲍曼不动杆菌分泌细胞毒性外膜蛋白通过外膜囊泡.pdfVIP

Acinetobacter baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles 1 2 1 1 1 2 Jong Sook Jin , Sang-Oh Kwon , Dong Chan Moon , Mamata Gurung , Jung Hwa Lee , Seung Il Kim *, Je Chul Lee1* 1 Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea, 2 Proteome Research Team, Korea Basic Science Institute, Daejeon, Korea Abstract Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606T secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606T induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the DompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N- terminal region