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

During infection, Brucella species have to adapt to a range of different en vironments. Environmental sensing in bacteria often involves the concerted action of two-component regulatory systems consisting of sensor and respons e 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 re gulator 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 r oles in nitrogen metabolism and potentially in virulence in other bacterial species. A B. suis ntrC isogenic mutant was constructed which showed no si gnificant 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 mu tation 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 t issue. (C) 1999 Academic Press.