Regulation and differential expression of gdhA encoding NADP-specific glutamate dehydrogenase in Neisseria meningitidis clinical isolates

Meningococcal gdhA, encoding the NADP-specific L- glutamate dehydrogenase (NADP-GDH), is essential for systemic infection in an infant rat model. In this paper, a limited transcriptional analysis detected differencesin gdhA expression among clinical isolates. In strains expressing high levels ofgdhA mRNA, two promoters,gdhA P1 and gdhA P2, initiated transcription of gdhA. In contrast, in strains expressing low mRNA levels,gdhA P2 was not active because of weak expression ofgdhR, an associated regulatorygene. Gene knock-out and complementation of agdhR-defective mutant confirmed that GdhR is a positive regulator forgdhA P2. Trans-activation ofgdhA P2 was maximal in complex medium during late logarithmicgrowth phase and in chemical defined medium (MCDA) when glucose (MCDA-glucose)instead of lactate (MCDA-lactate) was used as a carbonsource in the presence of glutamate. gdhR knockoutmutants lost both growth phase and carbon source regulation, and exhibited a growth defect moresevere in MCDA-glucose than in MCDA-lactate. DNA–protein interaction studies demonstrated that 2-oxoglutarate,a product of the catabolic reaction of theNADP-GDH and an intermediate of the tricarboxylicacid (TCA) cycle, inhibits binding of GdhR to gdhA P2.