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Nucleolar c-Myc recruitment by a Vibrio T3SS effector promotes host cell proliferation and bacterial virulence.
Hu, Maozhi; Zhang, Yibei; Gu, Dan; Chen, Xiang; Waldor, Matthew K; Zhou, Xiaohui.
Afiliação
  • Hu M; Department of Pathobiology and Veterinary Science, University of Connecticut, Mansfield, CT, USA.
  • Zhang Y; Department of Pathobiology and Veterinary Science, University of Connecticut, Mansfield, CT, USA.
  • Gu D; Department of Pathobiology and Veterinary Science, University of Connecticut, Mansfield, CT, USA.
  • Chen X; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Waldor MK; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Zhou X; Howard Hughes Medical Institute, Boston, MA, USA.
EMBO J ; 40(2): e105699, 2021 01 15.
Article em En | MEDLINE | ID: mdl-33347626
Pathogen type 3 secretion systems (T3SS) manipulate host cell pathways by directly delivering effector proteins into host cells. In Vibrio parahaemolyticus, the leading cause of bacterial seafood-borne diarrheal disease, we showed that a T3SS effector, VgpA, localizes to the host cell nucleolus where it binds Epstein-Barr virus nuclear antigen 1-binding protein 2 (EBP2). An amino acid substitution in VgpA (VgpAL10A ) did not alter its translocation to the nucleus but abolished the effector's capacity to interact with EBP2. VgpA-EBP2 interaction led to the re-localization of c-Myc to the nucleolus and increased cellular rRNA expression and proliferation of cultured cells. The VgpA-EBP2 interaction elevated EBP2's affinity for c-Myc and prolonged the oncoprotein's half-life. Studies in infant rabbits demonstrated that VgpA is translocated into intestinal epithelial cells, where it interacts with EBP2 and leads to nucleolar re-localization of c-Myc. Moreover, the in vivo VgpA-EBP2 interaction during infection led to proliferation of intestinal cells and heightened V. parahaemolyticus' colonization and virulence. These observations suggest that direct effector stimulation of a c-Myc controlled host cell growth program can contribute to pathogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Vibrio parahaemolyticus / Virulência / Nucléolo Celular / Proteínas Proto-Oncogênicas c-myc / Proliferação de Células / Sistemas de Secreção Tipo III Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Vibrio parahaemolyticus / Virulência / Nucléolo Celular / Proteínas Proto-Oncogênicas c-myc / Proliferação de Células / Sistemas de Secreção Tipo III Limite: Animals / Humans Idioma: En Revista: EMBO J Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos