Regulation of Denitrification Genes in Neisseria meningitidis by Nitric Oxide and the Repressor NsrR

ABSTRACT The human pathogen Neisseria meningitidis is capable of growth using the denitrification of nitrite to nitrous oxide under microaerobic conditions. This process is catalyzed by two reductases: nitrite reductase (encoded by aniA) and nitric oxide (NO) reductase (encoded by norB). Here, we show that in N. meningitidis MC58 norB is regulated by nitric oxide via the product of gene NMB0437 which encodes NsrR. NsrR is a repressor in the absence of NO, but norB expression is derepressed by NO in an NsrR-dependent manner. nsrR-deficient mutants grow by denitrification more rapidly than wild-type N. meningitidis, and this is coincident with the upregulation of both NO reductase and nitrite reductase even under aerobic conditions in the absence of nitrite or NO. The NsrR-dependent repression of aniA (unlike that of norB) is not lifted in the presence of NO. The role of NsrR in the control of expression of aniA is linked to the function of the anaerobic activator protein FNR: analysis of nsrR and fnr single and nsrR fnr double mutants carrying an aniA promoter lacZ fusion indicates that the role of NsrR is to prevent FNR-dependent aniA expression under aerobic conditions, indicating that FNR in N. meningitidis retains considerable activity aerobically.

[1]  Lori A. S. Snyder,et al.  Coordinated Regulation of the Neisseria gonorrhoeae-truncated Denitrification Pathway by the Nitric Oxide-sensitive Repressor, NsrR, and Nitrite-insensitive NarQ-NarP* , 2006, Journal of Biological Chemistry.

[2]  S. Nakano,et al.  The Nitric Oxide-Responsive Regulator NsrR Controls ResDE-Dependent Gene Expression , 2006, Journal of bacteriology.

[3]  G. Grandi,et al.  Role of FNR and FNR‐regulated, sugar fermentation genes in Neisseria meningitidis infection , 2006, Molecular microbiology.

[4]  F. Blattner,et al.  IscR‐dependent gene expression links iron‐sulphur cluster assembly to the control of O2‐regulated genes in Escherichia coli , 2006, Molecular microbiology.

[5]  D. Bodenmiller,et al.  The yjeB (nsrR) Gene of Escherichia coli Encodes a Nitric Oxide-Sensitive Transcriptional Regulator , 2006, Journal of bacteriology.

[6]  R. Read,et al.  Inhibition of Macrophage Apoptosis by Neisseria meningitidis Requires Nitric Oxide Detoxification Mechanisms , 2006, Infection and Immunity.

[7]  M. Anjum,et al.  The pathogen Neisseria meningitidis requires oxygen, but supplements growth by denitrification. Nitrite, nitric oxide and oxygen control respiratory flux at genetic and metabolic levels , 2005, Molecular microbiology.

[8]  N. Tucker,et al.  A non-haem iron centre in the transcription factor NorR senses nitric oxide , 2005, Nature.

[9]  Inna Dubchak,et al.  Dissimilatory Metabolism of Nitrogen Oxides in Bacteria: Comparative Reconstruction of Transcriptional Networks , 2005, PLoS Comput. Biol..

[10]  R. Read,et al.  Nitric Oxide Detoxification Systems Enhance Survival of Neisseria meningitidis in Human Macrophages and in Nasopharyngeal Mucosa , 2005, Infection and Immunity.

[11]  H. Westerhoff,et al.  Expression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel nitrite‐sensitive transcription repressor , 2004, Molecular microbiology.

[12]  R. Rappuoli,et al.  Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis , 2004, Molecular microbiology.

[13]  D. Touati,et al.  Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Guanghui Wu,et al.  NO sensing by FNR: regulation of the Escherichia coli NO‐detoxifying flavohaemoglobin, Hmp , 2002, The EMBO journal.

[15]  M. Anjum,et al.  Nitric Oxide Metabolism in Neisseria meningitidis , 2002, Journal of bacteriology.

[16]  P. Kiley,et al.  IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Virginia L. Clark,et al.  Gonococcal Nitric Oxide Reductase Is Encoded by a Single Gene, norB, Which Is Required for Anaerobic Growth and Is Induced by Nitric Oxide , 2000, Infection and Immunity.

[18]  Tim W. Overton,et al.  Identification of transcription activators that regulate gonococcal adaptation from aerobic to anaerobic or oxygen‐limited growth , 2000, Molecular microbiology.

[19]  S. Salzberg,et al.  Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. , 2000, Science.

[20]  J. V. D. van der Meer,et al.  Update on meningococcal disease with emphasis on pathogenesis and clinical management. , 2000, Clinical microbiology reviews.

[21]  P. Kiley,et al.  Oxygen sensing by the global regulator, FNR: the role of the iron-sulfur cluster. , 1998, FEMS microbiology reviews.

[22]  Robert G. Martin,et al.  A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Nejadnik,et al.  Nasal contribution to exhaled nitric oxide at rest and during breathholding in humans. , 1996, American journal of respiratory and critical care medicine.

[24]  V. Clark,et al.  Construction of a translational lacZ fusion system to study gene regulation in Neisseria gonorrhoeae. , 1995, Gene.

[25]  S. Tannenbaum,et al.  Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  A. Barlow,et al.  Point mutation in meningococcal por A gene associated with increased endemic disease , 1991, The Lancet.

[27]  F. Heffron,et al.  Shuttle mutagenesis of Neisseria gonorrhoeae: pilin null mutations lower DNA transformation competence , 1990, Journal of bacteriology.

[28]  S. Moncada,et al.  The Discovery of Nitric Oxide as the Endogenous Nitrovasodilator , 1988, Hypertension.

[29]  H. Krisch,et al.  In vitro insertional mutagenesis with a selectable DNA fragment. , 1984, Gene.

[30]  Jeffrey H. Miller Experiments in molecular genetics , 1972 .

[31]  D. Donald Determination of nitrate and nitrite , 1957 .

[32]  D. Nicholas,et al.  [144] Determination of nitrate and nitrite , 1957 .