Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity.
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.
Choi
Chul Hee
CH
Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea.
Hyun
Sung Hee
SH
Lee
Ji Young
JY
Lee
Jun Sik
JS
Lee
Yong Seok
YS
Kim
Soon Ae
SA
Chae
Jeong-Pil
JP
Yoo
Seung Min
SM
Lee
Je Chul
JC
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
D001425:Bacterial Outer Membrane Proteins; D019913:Nuclear Localization Signals; D037521:Virulence Factors; C078167:OMPA outer membrane proteins