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

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JournalBiochemical journal
DatePublished - 1 Jul 2012
Issue number1
Volume445
Number of pages11
Pages (from-to)69-79
Original languageEnglish

Abstract

The closely-related pathogenic Neisseria species N. meningitidis and N. gonorrhoeae are able to respire in the absence of oxygen, using nitrite as an alternative electron acceptor. Nitrite reductase (encoded by aniA) is tightly regulated by four transcriptional regulators: FNR, NarP, FUR and NsrR. The four regulators control expression of aniA in N. meningitidis by binding to specific and distinct regions of the promoter. We show here that FUR and NarP are both required for induction of expression of aniA in N. meningitidis, and that they bind adjacent to one another in a non-cooperative manner. Activation via FUR/NarP is dependent on their topological arrangement relative to the RNA polymerase binding site. Analysis of the sequence of the aniA promoters from multiple N. meningitidis and N. gonorrhoeae 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 in vitro DNA binding and the promoter activation in intact cells by key activators FNR (oxygen sensor) and NarP (which is activated by nitrite in N. meningitidis). The weak relative binding of FNR to the N. gonorrhoeae aniA promoter (compared to N. meningitidis) is compensated for by a higher affinity of the gonococcal aniA promoter for NarP. Despite containing nearly identical genes for catalysing and regulating denitrification, variations in the promoter for the aniA gene appear to have been selected to enable the two pathogens to tune differentially their responses to environmental variables during the aerobic-anaerobic switch.

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