Sec24 interaction is essential for localization and virulence-associated function of the bacterial effector protein NleA

Ajitha Thanabalasuriar, Julien Bergeron, Akira Gillingham, Mark Mimee, Jenny Lee Thomassin, Nathalie Strynadka, Jinoh Kim, Samantha Gruenheid

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) are food-borne pathogens that cause severe diarrhoeal disease in humans. Citrobacter rodentium is a related mouse pathogen that serves as a small animal model for EPEC and EHEC infections. EPEC, EHEC and C.rodentium translocate bacterial virulence proteins directly into host cells via a type III secretion system (T3SS). Non-LEE-encoded effector A (NleA) is a T3SS effector that is common to EPEC, EHEC and C.rodentium and is required for bacterial virulence. NleA localizes to the host cell secretory pathway and inhibits vesicle trafficking by interacting with the Sec24 subunit of mammalian coatamer protein II complex (COPII). Mammalian cells express four paralogues of Sec24 (Sec24A-D), which mediate selection of cargo proteins for transport and possess distinct, but overlapping cargo specificities. Here, we show that NleA binds Sec24A-D with two distinct mechanisms. An NleA protein variant with greatly diminished interaction with all Sec24 paralogues does not properly localize, does not inhibit COPII-mediated vesicle budding, and does not confer virulence in the mouse infection model. Together, this work provides strong evidence that the interaction and inhibition of COPII by NleA is an important aspect of EPEC- and EHEC-mediated disease.

Original languageEnglish (US)
Pages (from-to)1206-1218
Number of pages13
JournalCellular Microbiology
Volume14
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Enterohemorrhagic Escherichia coli
Enteropathogenic Escherichia coli
Bacterial Proteins
Virulence
Citrobacter rodentium
Proteins
Escherichia coli Infections
Secretory Pathway
Protein Transport
Animal Models
Food
Infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

Cite this

Thanabalasuriar, A., Bergeron, J., Gillingham, A., Mimee, M., Thomassin, J. L., Strynadka, N., ... Gruenheid, S. (2012). Sec24 interaction is essential for localization and virulence-associated function of the bacterial effector protein NleA. Cellular Microbiology, 14(8), 1206-1218. https://doi.org/10.1111/j.1462-5822.2012.01789.x

Sec24 interaction is essential for localization and virulence-associated function of the bacterial effector protein NleA. / Thanabalasuriar, Ajitha; Bergeron, Julien; Gillingham, Akira; Mimee, Mark; Thomassin, Jenny Lee; Strynadka, Nathalie; Kim, Jinoh; Gruenheid, Samantha.

In: Cellular Microbiology, Vol. 14, No. 8, 08.2012, p. 1206-1218.

Research output: Contribution to journalArticle

Thanabalasuriar, A, Bergeron, J, Gillingham, A, Mimee, M, Thomassin, JL, Strynadka, N, Kim, J & Gruenheid, S 2012, 'Sec24 interaction is essential for localization and virulence-associated function of the bacterial effector protein NleA', Cellular Microbiology, vol. 14, no. 8, pp. 1206-1218. https://doi.org/10.1111/j.1462-5822.2012.01789.x
Thanabalasuriar, Ajitha ; Bergeron, Julien ; Gillingham, Akira ; Mimee, Mark ; Thomassin, Jenny Lee ; Strynadka, Nathalie ; Kim, Jinoh ; Gruenheid, Samantha. / Sec24 interaction is essential for localization and virulence-associated function of the bacterial effector protein NleA. In: Cellular Microbiology. 2012 ; Vol. 14, No. 8. pp. 1206-1218.
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