Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis

Dara L. Burdette, Melanie L. Yarbrough, Anthony Orvedahl, Christopher J. Gilpin, Kim Orth

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion system to cause death of host cells within hours of infection. We report that cell death is completely independent of apoptosis and occurs by a mechanism in which injection of multiple type III effectors causes induction of autophagy, cell rounding, and the subsequent release of cellular contents. Autophagy is detected by the appearance of lipidated light chain 3 (LC3) and by increases in punctae and vacuole formation. Electron microscopy reveals the production of early autophagic vesicles during infection. Consistent with phosphoinositide 3 (PI3) kinase playing a role in autophagy, treatment of infected cells with a PI3 kinase inhibitor attenuates autophagy in infected cells. Because many effectors are injected during a V. parahaemolyticus infection, it is not surprising that the presence of a sole PI3 kinase inhibitor does not prevent inevitable host-cell death. Our studies reveal an infection paradigm whereby an extracellular pathogen uses its type III secretion system to cause at least three parallel events that eventually result in the proinflammatory death of an infected host cell.

Original languageEnglish (US)
Pages (from-to)12497-12502
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - Aug 26 2008

Fingerprint

Vibrio parahaemolyticus
Autophagy
1-Phosphatidylinositol 4-Kinase
Infection
Cell Death
Vibrio Infections
Vacuoles
Cause of Death
Electron Microscopy
Apoptosis
Light
Injections

Keywords

  • Apoptosis
  • Effector
  • Host-pathogen
  • Inflammatory
  • Type III secretion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Vibrio parahaemolyticus orchestrates a multifaceted host cell infection by induction of autophagy, cell rounding, and then cell lysis. / Burdette, Dara L.; Yarbrough, Melanie L.; Orvedahl, Anthony; Gilpin, Christopher J.; Orth, Kim.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 34, 26.08.2008, p. 12497-12502.

Research output: Contribution to journalArticle

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