title: A Vibrio parahaemolyticus T3SS effector mediates pathogenesis by independently enabling intestinal colonization and inhibiting TAK1 activation.
abstract: Vibrio parahaemolyticus type III secretion system 2 (T3SS2) is essential for the organism's virulence, but the effectors required for intestinal colonization and induction of diarrhea by this pathogen have not been identified. Here, we identify a type III secretion system (T3SS2)-secreted effector, VopZ, that is essential for V. parahaemolyticus pathogenicity. VopZ plays distinct, genetically separable roles in enabling intestinal colonization and diarrheagenesis. Truncation of VopZ prevents V. parahaemolyticus colonization, whereas deletion of VopZ amino acids 38-62 abrogates V. parahaemolyticus-induced diarrhea and intestinal pathology but does not impair colonization. VopZ inhibits activation of the kinase TAK1 and thereby prevents the activation of MAPK and NF-κB signaling pathways, which lie downstream. In contrast, the VopZ internal deletion mutant cannot counter the activation of pathways regulated by TAK1. Collectively, our findings suggest that VopZ's inhibition of TAK1 is critical for V. parahaemolyticus to induce diarrhea and intestinal pathology.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, 15 Francis Street, Boston, MA 02115, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Gewurz
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Ritchie
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takasaki
authors.forename: Hannah
authors.initials: H
authors.lastname: Greenfeld
authors.forename: Elliott
authors.initials: E
authors.lastname: Kieff
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D015398:Signal Transduction; D014162:Transfection; D014735:Vibrio Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014736:Vibrio parahaemolyticus / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D016328:NF-kappa B; D037521:Virulence Factors; D000099151:MAP Kinase Kinase Kinase 7