Neisseria meningitidis and Neisseria gonorrhoeae are differently adapted in the regulation of denitrification: single nucleotide polymorphisms that enable species-specific tuning of the aerobic–anaerobic switch

摘要

pThe closely related pathogenic iNeisseria/i species iN. meningitidis/i and iN. gonorrhoeae/i are able to respire in the absence of oxygen, using nitrite as an alternative electron acceptor. ianiA/i (copper-containing nitrite reductase) is tightly regulated by four transcriptional regulators: FNR (fumarate and nitrate reductase), NarP, FUR (Ferric uptake regulator) and NsrR. The four regulators control expression of ianiA/i in iN. meningitidis/i by binding to specific and distinct regions of the promoter. We show in the present study that FUR and NarP are both required for the induction of expression of ianiA/i in iN. meningitidis/i, and that they bind adjacent to one another in a non-co-operative manner. Activation via FUR/NarP is dependent on their topological arrangement relative to the RNA polymerase-binding site. Analysis of the sequence of the ianiA/i promoters from multiple iN. meningitidis/i and iN. gonorrhoeae/i strains indicates that there are species-specific single nucleotide polymorphisms, in regions predicted to be important for regulator binding. These sequence differences alter both the iin vitro/i DNA binding and the promoter activation in intact cells by key activators FNR (oxygen sensor) and NarP (which is activated by nitrite in iN. meningitidis/i). The weak relative binding of FNR to the iN. gonorrhoeae aniA/i promoter (compared to iN. meningitidis/i) is compensated for by a higher affinity of the gonococcal ianiA/i promoter for NarP. Despite containing nearly identical genes for catalysing and regulating denitrification, variations in the promoter for the ianiA/i gene appear to have been selected to enable the two pathogens to tune differentially their responses to environmental variables during the aerobic–anaerobic switch./p