The Bacterial Virulence Factor NleA Inhibits Cellular Protein Secretion by Disrupting Mammalian COPII Function

Jinoh Kim, Ajitha Thanabalasuriar, Tessa Chaworth-Musters, J. Chris Fromme, Elizabeth A. Frey, Paula I Lario, Pavel Metalnikov, Keyrillos Rizg, Nikhil A. Thomas, Sau Fung Lee, Elizabeth L. Hartland, Philip R Hardwidge, Tony Pawson, Natalie C. Strynadka, B. Brett Finlay, Randy Schekman, Samantha Gruenheid

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) maintain an extracellular lifestyle and use a type III secretion system to translocate effector proteins into the host cytosol. These effectors manipulate host pathways to favor bacterial replication and survival. NleA is an EHEC/EPEC- and related species-specific translocated effector protein that is essential for bacterial virulence. However, the mechanism by which NleA impacts virulence remains undetermined. Here we demonstrate that NleA compromises the Sec23/24 complex, a component of the mammalian COPII protein coat that shapes intracellular protein transport vesicles, by directly binding Sec24. Expression of an NleA-GFP fusion protein reduces the efficiency of cellular secretion by 50%, and secretion is inhibited in EPEC-infected cells. Direct biochemical experiments show that NleA inhibits COPII-dependent protein export from the endoplasmic reticulum. Collectively, these findings indicate that disruption of COPII function in host cells contributes to the virulence of EPEC and EHEC.

Original languageEnglish (US)
Pages (from-to)160-171
Number of pages12
JournalCell Host and Microbe
Volume2
Issue number3
DOIs
StatePublished - Sep 13 2007

Keywords

  • MICROBIO
  • PROTEINS

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Fingerprint Dive into the research topics of 'The Bacterial Virulence Factor NleA Inhibits Cellular Protein Secretion by Disrupting Mammalian COPII Function'. Together they form a unique fingerprint.

  • Cite this

    Kim, J., Thanabalasuriar, A., Chaworth-Musters, T., Fromme, J. C., Frey, E. A., Lario, PI., Metalnikov, P., Rizg, K., Thomas, N. A., Lee, S. F., Hartland, E. L., Hardwidge, PR., Pawson, T., Strynadka, N. C., Finlay, B. B., Schekman, R., & Gruenheid, S. (2007). The Bacterial Virulence Factor NleA Inhibits Cellular Protein Secretion by Disrupting Mammalian COPII Function. Cell Host and Microbe, 2(3), 160-171. https://doi.org/10.1016/j.chom.2007.07.010