title: Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity.
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 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.
authors.affiliation: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Chul Hee
authors.initials: CH
authors.lastname: Choi
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Soon Ae
authors.initials: SA
authors.lastname: Kim
authors.forename: Jeong-Pil
authors.initials: JP
authors.lastname: Chae
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Yoo
authors.forename: Je Chul
authors.initials: JC
authors.lastname: Lee
mesh_terms: D040981:Acinetobacter baumannii / Q000378:metabolism / Q000472:pathogenicity*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000382:microbiology*; D002522:Chlorocebus aethiops; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000382:microbiology; D047108:Embryonic Development; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000382:microbiology; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000502:physiology; D020298:U937 Cells; D037521:Virulence Factors / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D001425:Bacterial Outer Membrane Proteins; D019913:Nuclear Localization Signals; D037521:Virulence Factors; C078167:OMPA outer membrane proteins