title: Importance of fumarate and nitrate reduction regulatory protein for intestinal proliferation of Vibrio vulnificus.
abstract: The sepsis caused by Vibrio vulnificus is characterized by an average incubation period of 26 h and a high mortality rate exceeding 50%. The fast growth and dissemination of V. vulnificus in vivo lead to poor clinical outcomes in patients. Therefore, elucidation of the proliferation mechanisms of this organism in vivo may lead to the development of an effective therapeutic strategy. In this study, we focused on the low oxygen concentration in the intestinal milieu because of its drastic difference from that in air. Fumarate and nitrate reduction regulatory protein (FNR) is known to be a global transcriptional regulator for adaptation to anaerobic conditions in various bacteria. We generated a strain of V. vulnificus in which the fnr gene was replaced with an erythromycin resistance gene (fnr::erm mutant). When the fnr::erm mutant was tested in a growth competition assay against the wild-type (WT) in vivo, the competitive index of fnr::erm mutant to WT in the intestinal loop and liver was 0.378 ± 0.192 (mean ± SD) and 0.243 ± 0.123, respectively. These data suggested that FNR is important for the proliferation of V. vulnificus in the intestine to achieve a critical mass to be able to invade the systemic circulation.
authors.affiliation: Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada Aomori 034-8628, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kado
authors.affiliation: Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada Aomori 034-8628, Japan kashimot@vmas.kitasato-u.ac.jp.
authors.forename: Takashige
authors.initials: T
authors.lastname: Kashimoto
authors.affiliation: Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada Aomori 034-8628, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Veterinary Public Health, School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada Aomori 034-8628, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D004926:Escherichia coli / Q000235:genetics; D005650:Fumarates / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D009154:Mutation; D009566:Nitrates / Q000378:metabolism*; D010084:Oxidation-Reduction; D018805:Sepsis / Q000382:microbiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D041261:Vibrio vulnificus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D005650:Fumarates; D009566:Nitrates; D014157:Transcription Factors
keywords: FNR; V. vulnificus; Vibrio; intestinal proliferation