Role of GlnR in Controlling Expression of Nitrogen Metabolism Genes in .

is a fastidious bacterial pathogen that can utilize only a limited number of nitrogen sources for growth. Both glutamine and ammonium are common nitrogen sources used in listerial defined growth media, but little is known about the regulation of their uptake or utilization. The functional role of GlnR, the transcriptional regulator of nitrogen metabolism genes in low-G+C Gram-positive bacteria, was determined using transcriptome sequencing and real-time reverse transcription-PCR experiments. The GlnR regulon included transcriptional units involved in ammonium transport () and biosynthesis of glutamine () and glutamate () from ammonium. As in other bacteria, GlnR proved to be an autoregulatory repressor of the operon. Unexpectedly, GlnR was most active during growth with ammonium as the nitrogen source and less active in the glutamine medium, apparently because listerial cells perceive growth with glutamine as a nitrogen-limiting condition. Therefore, paradoxically, expression of the gene, encoding glutamine synthetase, was highest in the glutamine medium. For the operon, GlnR served as both a negative regulator in the presence of ammonium and a positive regulator in the glutamine medium. The gene was subject to a third mode of regulation that apparently required an elevated level of GlnR for repression. Finally, activity of glutamate dehydrogenase encoded by the gene appeared to correlate inversely with expression of , the operon that encodes the other major glutamate-synthesizing enzyme, glutamate synthase. Both and were also regulated, in a negative manner, by the global transcriptional regulator CodY. is a widespread foodborne pathogen. Nitrogen-containing compounds, such as the glutamate-containing tripeptide, glutathione, and glutamine, have been shown to be important for expression of virulence genes. In this work, we showed that a transcriptional regulator, GlnR, controls expression of critical listerial genes of nitrogen metabolism that are involved in ammonium uptake and biosynthesis of glutamine and glutamate. A different mode of GlnR-mediated regulation was found for each of these three pathways.