title: The two-component systems PrrBA and NtrYX co-ordinately regulate the adaptation of Brucella abortus to an oxygen-limited environment.
abstract: Brucella is the causative agent of the zoonotic disease brucellosis, which is endemic in many parts of the world. The success of Brucella as pathogen relies in its ability to adapt to the harsh environmental conditions found in mammalian hosts. One of its main adaptations is the induction of the expression of different genes involved in respiration at low oxygen tension. In this report we describe a regulatory network involved in this adaptation. We show that Brucella abortus PrrBA is a functional two-component signal transduction system that responds to the redox status and acts as a global regulator controlling the expression of the regulatory proteins NtrY, FnrN and NnrA, which are involved in the adaptation to survive at low oxygen tension. We also show that the two-component systems PrrBA and NtrYX co-ordinately regulate the expression of denitrification and high-affinity cytochrome oxidase genes. Strikingly, a double mutant strain in the prrB and ntrY genes is severely impaired in growth and virulence, while the ntrY and prrB single mutant strains are similar to wild-type B. abortus. The proposed regulatory network may contribute to understand the mechanisms used by Brucella for a successful adaptation to its replicative niche inside mammalian cells.
authors.affiliation: Laboratorio de Inmunología y Microbiología Molecular, Fundación Instituto Leloir (IIBBA-CONICET), Av. Patricias Argentinas 435, 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: Rodrigo
authors.initials: R
authors.lastname: Sieira
authors.forename: Gastón
authors.initials: G
authors.lastname: Paris
authors.forename: Fernando Alberto
authors.initials: FA
authors.lastname: Goldbaum
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002003:Brucella abortus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002006:Brucellosis / Q000382:microbiology; D058440:Denitrification; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D051379:Mice; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D003576:Electron Transport Complex IV; D011494:Protein Kinases; D000071677:Histidine Kinase; D010100:Oxygen