title: The NtrY/X two-component system of Brucella spp. acts as a redox sensor and regulates the expression of nitrogen respiration enzymes.
abstract: Brucella spp. are facultative intracellular bacteria pathogenic for many mammalian species including humans, causing a disease called brucellosis. Learning how Brucella adapts to its intracellular niche is crucial for understanding its pathogenesis mechanism, allowing for the development of new and more effective vaccines and treatments against brucellosis. Brucella pathogenesis resides mostly in its ability to adapt to the harsh environmental conditions encountered during host infection such as the oxygen depletion. The mechanism by which Brucella senses the oxygen tension and triggers its environmental adaptation is unknown. In this work we show that the Brucella abortus NtrY/NtrX two-component system is involved in oxygen sensing through a haem group contained in a Per-ARNT-SIM (PAS) domain of the NtrY histidine kinase. The NtrY haem iron can be reduced to the ferrous form and is rapidly oxidized to the ferric form in presence of oxygen. Importantly, we show that the oxidation state of the haem iron modulates the autokinase activity, being the anoxygenic reduced ferrous form the signalling state of NtrY. Also, we show that ntrY gene expression increases under low oxygen tension and that NtrY transfers its signal to its cognate response regulator NtrX, regulating in this way the expression of nitrogen respiration enzymes. Based on these findings, we postulate that NtrY acts as a redox sensor in Brucella spp.
authors.affiliation: Fundación Instituto Leloir (IIBBA-CONICET), Buenos Aires, Argentina.
authors.forename: Mariela del Carmen
authors.initials: Mdel C
authors.lastname: Carrica
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernandez
authors.forename: Marcelo Adrián
authors.initials: MA
authors.lastname: Martí
authors.forename: Gastón
authors.initials: G
authors.lastname: Paris
authors.forename: Fernando Alberto
authors.initials: FA
authors.lastname: Goldbaum
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002003:Brucella abortus / Q000201:enzymology / Q000235:genetics*; D002460:Cell Line; D058440:Denitrification; D015964:Gene Expression Regulation, Bacterial; D006418:Heme / Q000378:metabolism; D000071677:Histidine Kinase; D051379:Mice; D009584:Nitrogen / Q000378:metabolism*; D009876:Operon; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D006418:Heme; D011494:Protein Kinases; D000071677:Histidine Kinase; D009584:Nitrogen; D010100:Oxygen