Title

Gene regulation by redox-sensitive Burkholderia thailandensis OhrR and its role in bacterial killing of Caenorhabditis elegans

Document Type

Article

Publication Date

9-1-2018

Abstract

© 2018 American Society for Microbiology. Fatty acid hydroperoxides are involved in host-pathogen interactions. In both plants and mammals, polyunsaturated fatty acids are liberated during infection and enzymatically oxidized to the corresponding toxic hydroperoxides during the defensive oxidative burst that is designed to thwart the infection. The bacterial transcription factor OhrR (organic hydroperoxide reductase regulator) is oxidized by organic hydroperoxides, as a result of which the ohr gene encoding organic hydroperoxide reductase is induced. This enzyme converts the hydroperoxides to less toxic alcohols. We show here that OhrR from Burkholderia thailandensis represses expression of ohr. Gene expression is induced by cumene hydroperoxide and to a lesser extent by inorganic oxidants; however, Ohr contributes to degradation only of the organic hydroperoxide. B. thailandensis OhrR, which binds specific sites in both ohr and ohrR promoters, as evidenced by DNase I footprinting, belongs to the 2-Cys subfamily of OhrR proteins, and its oxidation leads to reversible disulfide bond formation between conserved N- and C-terminal cysteines in separate monomers. Oxidation of the N-terminal Cys is sufficient for attenuation of DNA binding in vitro, with complete restoration of DNA binding occurring on addition of a reducing agent. Surprisingly, both overexpression of ohr and deletion of ohr results in enhanced survival on exposure to organic hydroperoxide in vitro. While Δohr cells are more virulent in a Caenorhabditis elegans model of infection, ΔohrR cells are less so. Taken together, our data suggest that B. thailandensis OhrR has several unconventional features and that both OhrR and organic hydroperoxides may contribute to virulence.

Publication Source (Journal or Book title)

Infection and Immunity

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