Investigation into the role of the response regulator NtrC in the metabolism and virulence ofBrucella suis

During infection,Brucellaspecies 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 fromBrucella 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. AB. suis ntrCisogenic mutant was constructed which showed no significant differences in growth rates compared to the wild-type strain when grown at different temperaturesin 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 ofB. suisin macrophages, but during the initial stages of infection in the murine brucellosis model, thentrCmutant showed a reduced ability to multiply rapidly in splenic tissue.