title: Investigation into the role of the response regulator NtrC in the metabolism and virulence of Brucella suis.
abstract: During infection, Brucella species have to adapt to a range of different environments. Environmental sensing in bacteria often involves the concerted action of two-component regulatory systems consisting of sensor and response regulator components. In this study, we identified, cloned and sequenced four independent response regulator gene fragments from Brucella melitensis. One amplified gene fragment showed nearly 90% identity to the response regulator subfamily of NtrC transcriptional activators, and further analysis revealed the presence of an adjacent gene encoding the sensor protein NtrB. The NtrBC two-component regulatory system has been shown to play varying roles in nitrogen metabolism and potentially in virulence in other bacterial species. A B. suis ntrC isogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperatures in vitro. However, the mutant exhibited a reduction in metabolic activity in the presence of many amino acids. The mutation did not affect survival or multiplication of B. suis in macrophages, but during the initial stages of infection in the murine brucellosis model, the ntrC mutant showed a reduced ability to multiply rapidly in splenic tissue.
authors.affiliation: Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, West Smithfield, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Dorrell
authors.forename: P
authors.initials: P
authors.lastname: Guigue-Talet
authors.forename: S
authors.initials: S
authors.lastname: Spencer
authors.forename: V
authors.initials: V
authors.lastname: Foulonge
authors.forename: D
authors.initials: D
authors.lastname: O'Callaghan
authors.forename: B W
authors.initials: BW
authors.lastname: Wren
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins; D001483:Base Sequence; D002002:Brucella / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D017347:Brucella melitensis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D002006:Brucellosis / Q000382:microbiology*; D002241:Carbohydrates / Q000737:chemistry; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005562:Formazans / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016296:Mutagenesis; D051922:PII Nitrogen Regulatory Proteins; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013778:Tetrazolium Salts / Q000737:chemistry; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D014774:Virulence
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D002241:Carbohydrates; D017931:DNA Primers; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D005562:Formazans; D051922:PII Nitrogen Regulatory Proteins; D013778:Tetrazolium Salts; D015534:Trans-Activators; D014157:Transcription Factors; C079782:MTT formazan