@article{mbs:/content/journal/micro/10.1099/mic.0.024919-0, author = "Zhou, Xiaohui and Konkel, Michael E. and Call, Douglas R.", title = "Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines", journal= "Microbiology", year = "2009", volume = "155", number = "3", pages = "837-851", doi = "https://doi.org/10.1099/mic.0.024919-0", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.024919-0", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", keywords = "AO, acridine orange", keywords = "IL, interleukin", keywords = "LDH, lactate dehydrogenase", keywords = "STS, staurosporine", keywords = "MDC, monodansylcadaverine", keywords = "PARP, poly ADP ribose polymerase", keywords = "TBH, t-butylhydroperoxide", keywords = "T3SS, type III secretion system", 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.", }