The nitric oxide sensing repressor NsrR of Neisseria meningitidis has a compact regulon of genes involved in NO synthesis and detoxification

Department of Biology (Area 10), University of York, Heslington, York, YO10 5YW, UK

^* To whom correspondence should be addressed. Email: jm46{at}york.ac.uk.

	Abstract

We have analysed the extent of regulation by the NO-sensitive repressor NsrR from Neisseria meningitidis MC58 using microarrays. Target genes that appeared to be regulated by NsrR from comparison of an nsrR mutant versus a wild-type strain were further investigated by quantitative real time PCR revealing a very compact set of genes: namely, norB (encoding nitric oxide reductase), dnrN (encoding a protein putatively involved in repair of nitrosative damage to iron-sulfur clusters), aniA (encoding nitrite reductase), nirV (a putative nitrite reductase assembly protein), and mobA (a gene associated with molybdenum metabolism in other species but with a frame-shift in N. meningitidis). In all cases NsrR acts as a repressor. NO protection systems norB and dnrN are regulated by NO in an NsrR dependent manner, whereas the NO protection system cytochrome c' (encoded by cycP) is not controlled by NO or NsrR, indicating that N. meningitidis expresses both constitutive and inducible NO protection systems. In addition, we present evidence that the anaerobic-response regulator FNR is also sensitive to NO, but less than NsrR, resulting in complex regulation of promoters such as the one of aniA controlled by both FNR and NsrR: aniA was found to be maximally induced by intermediate NO concentrations, consistent with a regulatory system that allows expression during denitrification (in which NO accumulates) but down-regulation as NO approaches toxic concentrations.