title: Nitric oxide-enhanced Shiga toxin production was regulated by Fur and RecA in enterohemorrhagic Escherichia coli O157.
abstract: Enterohemorrhagic Escherichia coli (EHEC) produces Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). Nitric oxide (NO), which acts as an antimicrobial defense molecule, was found to enhance the production of Stx1 and Stx2 in EHEC under anaerobic conditions. Although EHEC O157 has two types of anaerobic NO reductase genes, an intact norV and a deleted norV, in the deleted norV-type EHEC, a high concentration of NO (12-29 μmol/L, maximum steady-state concentration) is required for enhanced Stx1 production and a low concentration of NO (~12 μmol/L, maximum steady-state concentration) is sufficient for enhanced Stx2 production under anaerobic conditions. These results suggested that different concentration thresholds of NO elicit a discrete set of Stx1 and Stx2 production pathways. Moreover, the enhancement of Shiga toxin production in the intact norV-type EHEC required treatment with a higher concentration of NO than was required for enhancement of Shiga toxin production in the deleted norV-type EHEC, suggesting that the specific NorV type plays an important role in the level of enhancement of Shiga toxin production in response to NO. Finally, Fur derepression and RecA activation in EHEC were shown to participate in the NO-enhanced Stx1 and Stx2 production, respectively.
authors.affiliation: Departments of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Ichimura
authors.affiliation: Departments of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.identifier: 0000-0001-8865-1884
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Pharmacology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Division of Bacteriology, Chiba Prefectural Institute of Public Health, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hirai
authors.affiliation: Division of Bacteriology, Chiba Prefectural Institute of Public Health, Chiba, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yokoyama
authors.affiliation: Departments of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Departments of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kinnosuke
authors.initials: K
authors.lastname: Yahiro
authors.affiliation: Departments of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Noda
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000378:metabolism*; D019453:Escherichia coli O157 / Q000187:drug effects* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009569:Nitric Oxide / Q000378:metabolism*; D011938:Rec A Recombinases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D022621:Shiga Toxin / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D009569:Nitric Oxide; D022621:Shiga Toxin; D011938:Rec A Recombinases
keywords: Fur; NO reductase; RecA; Shiga toxin; enterohemorrhagic Escherichia coli; nitric oxide