Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells.
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.
Choi
Chul Hee
CH
Department of Microbiology, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
Lee
Eun Young
EY
Lee
Yoo Chul
YC
Park
Tae In
TI
Kim
Hwa Jung
HJ
Hyun
Sung Hee
SH
Kim
Soon Ae
SA
Lee
Seong-Kyu
SK
Lee
Je Chul
JC
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
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D001425:Bacterial Outer Membrane Proteins; D045304:Cytochromes c; D020169:Caspases