Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity |
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Authors: | 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 |
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Institution: | Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea.; Department of Biomedical Laboratory Science, Eulji University, School of Medicine, Daejeon, Korea.; Department of Parasitology and Malariology, PICR, College of Medicine and Frontier Inje Research for Science and Technology, Inje University, Busan, Korea.; Department of Pharmacology, Eulji University, School of Medicine, Daejeon, Korea.; Departments of Anatomy, Kyungpook National University School of Medicine, Daegu, Korea.; Microbiology, Eulji University, School of Medicine, Daejeon, Korea. |
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Abstract: | 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 AbOmpAΔNLS–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. |
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