title: RtxA1-induced expression of the small GTPase Rac2 plays a key role in the pathogenicity of Vibrio vulnificus.
abstract: Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P)H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus.
authors.affiliation: School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chonnam National University, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Chung
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Cho
authors.forename: Mi Kwang
authors.initials: MK
authors.lastname: Kim
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Kim
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Yang
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Chung
authors.forename: Shee Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Rhee
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D051379:Mice; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species / Q000378:metabolism; D014735:Vibrio Infections / Q000382:microbiology*; D041261:Vibrio vulnificus / Q000378:metabolism / Q000472:pathogenicity*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D001427:Bacterial Toxins; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C434464:RtxA protein, Vibrio cholerae; C402799:NOX1 protein, human