title: The Vibrio parahaemolyticus effector VopC mediates Cdc42-dependent invasion of cultured cells but is not required for pathogenicity in an animal model of infection.
abstract: Vibrio parahaemolyticus is a Gram-negative marine bacterium that causes acute gastroenteritis in humans. The virulence of V. parahaemolyticus is dependent upon a type III secretion system (T3SS2). One effector for T3SS2, VopC, is a homologue of the catalytic domain of cytotoxic necrotizing factor (CNF), and was recently reported to be a Rho family GTPase activator and to be linked to internalization of V. parahaemolyticus by non-phagocytic cultured cells. Here, we provide direct evidence that VopC deamidates Rac1 and CDC42, but not RhoA, in vivo. Our results alsosuggest that VopC, through its activation of Rac1, contributes to formation of actin stress fibres in infected cells. Invasion of host cells, which occurs at a low frequency, does not seem linked to Rac1 activation, but instead appears to require CDC42. Finally, using an infant rabbit model of V. parahaemolyticus infection, we show that the virulence of V. parahaemolyticus is not dependent upon VopC-mediated invasion. Genetic inactivation of VopC did not impair intestinal colonization nor reduce signs of disease, including fluid accumulation, diarrhoea and tissue destruction. Thus, although VopC can promote host cell invasion, such internalization is not a critical step of the disease process, consistent with the traditional view of V. parahaemolyticus as an extracellular pathogen.
authors.affiliation: Laboratory of Genomic Research on Pathogenic Bacteria, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Ryu
authors.initials: R
authors.lastname: Okada
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Hiyoshi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Matsuda
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.forename: Takashige
authors.initials: T
authors.lastname: Kashimoto
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
authors.forename: Toshio
authors.initials: T
authors.lastname: Kodama
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D011817:Rabbits; D014735:Vibrio Infections / Q000382:microbiology* / Q000473:pathology; D014736:Vibrio parahaemolyticus / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein