Choi Chul Hee, Hyun Sung Hee, Lee Ji Young, Lee Jun Sik, Lee Yong Seok, Kim Soon Ae, Chae Jeong-Pil, Yoo Seung Min, Lee Je Chul
Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea.
Cell Microbiol. 2008 Feb;10(2):309-19. doi: 10.1111/j.1462-5822.2007.01041.x. Epub 2007 Aug 30.
Acinetobacter baumannii is an emerging opportunistic pathogen responsible for healthcare-associated infections. The outer membrane protein A of A. baumannii (AbOmpA) is the most abundant surface protein that has been associated with the apoptosis of epithelial cells through mitochondrial targeting. The nuclear translocation of AbOmpA and the subsequent pathology on host cells were further investigated. AbOmpA directly binds to eukaryotic cells. AbOmpA translocates to the nucleus by a novel monopartite nuclear localization signal (NLS). The introduction of rAbOmpA into the cells or a transient expression of AbOmpA-EGFP causes the nuclear localization of these proteins, while the fusion proteins of AbOmpADeltaNLS-EGFP and AbOmpA with substitutions in residues lysine to alanine in the NLS sequences represent an exclusively cytoplasmic distribution. The nuclear translocation of AbOmpA induces cell death in vitro. Furthermore, the microinjection of rAbOmpA into the nucleus of Xenopus laevis embryos fails to develop normal embryogenesis, thus leading to embryonic death. We propose a novel pathogenic mechanism of A. baumannii regarding the nuclear targeting of the bacterial structural protein AbOmpA.
鲍曼不动杆菌是一种新出现的机会致病菌，可引起医疗保健相关感染。鲍曼不动杆菌的外膜蛋白A（AbOmpA）是最丰富的表面蛋白，它通过靶向线粒体与上皮细胞凋亡有关。对AbOmpA的核转位及随后对宿主细胞的病理作用进行了进一步研究。AbOmpA直接与真核细胞结合。AbOmpA通过一种新的单分型核定位信号（NLS）转位至细胞核。将重组AbOmpA导入细胞或瞬时表达AbOmpA-EGFP会导致这些蛋白的核定位，而AbOmpADeltaNLS-EGFP和在NLS序列中赖氨酸残基被替换为丙氨酸的AbOmpA融合蛋白则仅分布于细胞质中。AbOmpA的核转位在体外诱导细胞死亡。此外，将重组AbOmpA显微注射到非洲爪蟾胚胎细胞核中会导致胚胎无法正常发育，从而导致胚胎死亡。我们提出了一种关于鲍曼不动杆菌细菌结构蛋白AbOmpA核靶向作用的新致病机制。
