RtxA1-induced expression of the small GTPase Rac2 plays a key role in the pathogenicity of Vibrio vulnificus.
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.
Chung
Kyoung-Jin
KJ
School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chonnam National University, Republic of Korea.
Cho
Eun-Jin
EJ
Kim
Mi Kwang
MK
Kim
Young Ran
YR
Kim
Seok-Ho
SH
Yang
Hee-Young
HY
Chung
Ki-Chul
KC
Lee
Shee Eun
SE
Rhee
Joon Haeng
JH
Choy
Hyon E
HE
Lee
Tae-Hoon
TH
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
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