Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells

被引:236
作者
Choi, CH
Lee, EY
Lee, YC
Park, TI
Kim, HJ
Hyun, SH
Kim, SA
Lee, SK
Lee, JC [1 ]
机构
[1] Kyungpook Natl Univ, Sch Med, Dept Microbiol, Taegu 700422, South Korea
[2] Kyungpook Natl Univ, Sch Med, Inst Infect Dis, Taegu 700422, South Korea
[3] Kyungpook Natl Univ, Sch Med, Dept Pathol, Taegu 700422, South Korea
[4] Chungnam Natl Univ, Coll Med, Dept Microbiol, Taejon 301747, South Korea
[5] Eulji Univ, Sch Med, Dept Clin Pathol, Taejon 301832, South Korea
[6] Eulji Univ, Sch Med, Dept Pharmacol, Taejon 301832, South Korea
[7] Eulji Univ, Sch Med, Dept Biochem, Taejon 301832, South Korea
关键词
D O I
10.1111/j.1462-5822.2005.00538.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1127 / 1138
页数:12
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