Ability of Brucella melitensis 16M to Control Nitrogen Process: Identification of a Novel P-II Family Nitrogen Regulator

Brucella spp. is a bacterium that can survive under conditions of nutrient starvation and is responsible for foodborne illnesses. The OmpR-type transcriptional regulator is characterized by an N-terminal receiver domain and a C-terminal domain, and it plays a regulatory role in diverse physiological processes, notably nitrogen and carbon metabolism. The genome of Brucella melitensis 16M contains genes for multiple OmpR-family regulators. However, the genetic program associated with nitrogen metabolism remains elusive. Herein, it was demonstrated that the B. melitensis 16M ΔftcR mutant, which lacks the OmpR-type regulator FtcR, displayed compromised viability upon recovery in a nitrogen- and carbon-free medium. Chromatin immunoprecipitation and next-generation sequencing were used to characterize the DNA-binding sites of FtcR. Our genome-wide analysis revealed extensive FtcR-binding sites throughout the B. melitensis 16M genome, including the identification of glnB as a novel target. As glnB encodes a P-II nitrogen regulator, this suggests FtcR plays a direct role in modulating nitrogen, carbon, and energy metabolism under prolonged nutrient starvation. In summary, our findings not only advance our understanding of the transcriptional regulation of nitrogen metabolism but also highlight its critical role in brucellosis pathogenesis, thereby paving the way for the development of novel therapeutics.