Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells
Outer membrane protein 38 of Acinetobacter baumannii localizes to the mitochondria and induces apoptosis of epithelial cells
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DOI：
10.1111/j.1462-5822.2005.00538.x
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发表时间：
2005-08-01
影响因子：
3.4
通讯作者：
Lee, JC
中科院分区：
文献类型：
--
作者：
Choi, CH;Lee, EY;Lee, JC
鲍曼不动杆菌是引起医院感染的重要条件致病菌。尽管有大量关于鲍曼不动杆菌在医院感染中的作用的临床和流行病学数据，但这种生物的具体毒力因素或致病机制尚未阐明。本研究探讨鲍曼不动杆菌感染人喉部上皮HEp-2细胞导致细胞凋亡的分子机制，并检测鲍曼不动杆菌外膜蛋白38 （Omp38）在鲍曼不动杆菌诱导上皮细胞凋亡中的作用。鲍曼杆菌通过细胞表面死亡受体和线粒体解体诱导HEp-2细胞凋亡。缺乏omp38的突变体诱导细胞凋亡的能力不如野生型鲍曼不动杆菌。纯化后的Omp38进入细胞并定位于线粒体，导致细胞色素c和凋亡诱导因子（AIF）等促凋亡分子的释放。由caspase-9激活的caspase-3的激活，降解了大约180 bp大小的DNA，这导致了一个特征DNA阶梯的出现。AIF降解了大约50 kb大小的染色体DNA，导致大规模的DNA片段化。这些结果表明，Omp38可能是鲍曼不动杆菌感染早期诱导上皮细胞凋亡的潜在毒力因子。
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.