title: Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells.
abstract: Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial infection. Despite considerable clinical and epidemiological data regarding the role of A. baumannii in nosocomial infection, the specific virulence factor or pathogenic mechanism of this organism has yet to be elucidated. This study investigated the molecular mechanism of apoptosis on the infection of human laryngeal epithelial HEp-2 cells with A. baumannii and examined the contribution of outer membrane protein 38 (Omp38) on the ability of A. baumannii to induce apoptosis of epithelial cells. A. baumannii induced apoptosis of HEp-2 cells through cell surface death receptors and mitochondrial disintegration. The Omp38-deficient mutant was not as able to induce apoptosis as the wild-type A. baumannii strain. Purified Omp38 entered the cells and was localized to the mitochondria, which led to a release of proapoptotic molecules such as cytochrome c and apoptosis-inducing factor (AIF). The activation of caspase-3, which is activated by caspase-9, degraded DNA approximately 180 bp in size, which resulted in the appearance of a characteristic DNA ladder. AIF degraded chromosomal DNA approximately 50 kb in size, which resulted in large-scale DNA fragmentation. These results demonstrate that Omp38 may act as a potential virulence factor to induce apoptosis of epithelial cells in the early stage of A. baumannii infection.
authors: Department of Microbiology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
authors: Chul Hee
authors: CH
authors: Choi
authors: Eun Young
authors: EY
authors: Lee
authors: Yoo Chul
authors: YC
authors: Lee
authors: Tae In
authors: TI
authors: Park
authors: Hwa Jung
authors: HJ
authors: Kim
authors: Sung Hee
authors: SH
authors: Hyun
authors: Soon Ae
authors: SA
authors: Kim
authors: Seong-Kyu
authors: SK
authors: Lee
authors: Je Chul
authors: JC
authors: Lee
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D001425:Bacterial Outer Membrane Proteins; D045304:Cytochromes c; D020169:Caspases