Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines.

Abstract

The Vibrio parahaemolyticus type III secretion system 1 (T3SS1) induces cytotoxicity in mammalian epithelial cells. We characterized the cell death phenotype in both epithelial (HeLa) and monocytic (U937) cell lines following infection with V. parahaemolyticus. Using a combination of the wild-type strain and gene knockouts, we confirmed that V. parahaemolyticus strain NY-4 was able to induce cell death in both cell lines via a T3SS1-dependent mechanism. Bacterial contact, but not internalization, was required for T3SS1-induced cytotoxicity. The mechanism of cell death involves formation of a pore structure on the surface of infected HeLa and U937 cells, as demonstrated by cellular swelling, uptake of cell membrane-impermeable dye and protection of cytotoxicity by osmoprotectant (PEG3350). Western blot analysis showed that poly ADP ribose polymerase (PARP) was not cleaved and remained in its full-length active form. This result was evident for seven different V. parahaemolyticus strains. V. parahaemolyticus-induced cytotoxicity was not inhibited by addition of the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) or the caspase-1 inhibitor N-acetyl-tyrosyl-valyl-alanyl-aspartyl-aldehyde (Ac-YVAD-CHO); thus, caspases were not involved in T3SS1-induced cytotoxicity. DNA fragmentation was not evident following infection and autophagic vacuoles were not observed after monodansylcadaverine staining. We conclude that T3SS1 of V. parahaemolyticus strain NY-4 induces a host cell death primarily via oncosis rather than apoptosis, pyroptosis or autophagy.

• Authors: Xiaohui Zhou, Michael E Konkel, Douglas R Call
• Journal: Microbiology (Reading, England) (Microbiology (Reading)) Vol. 155 Issue Pt 3 Pg. 837-851 (Mar 2009) ISSN: 1350-0872 [Print] England
• PMID: 19246755 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Caspase Inhibitors
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Autophagy
• Bacterial Proteins (metabolism)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Death (drug effects, genetics)
• Epithelial Cells (microbiology, ultrastructure)
• HeLa Cells
• Humans
• Microscopy, Electron, Transmission
• Monocytes (microbiology, ultrastructure)
• Poly(ADP-ribose) Polymerases (metabolism)
• U937 Cells
• Vibrio Infections (genetics)
• Vibrio parahaemolyticus (genetics, metabolism, pathogenicity)