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Journal of Bacteriology, December 2008, p. 7847-7858, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00905-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Characterization of the Oxygen-Responsive NreABC Regulon of Staphylococcus aureus{triangledown} ,{dagger}

Steffen Schlag,1,{ddagger} Stephan Fuchs,2,{ddagger} Christiane Nerz,1 Rosmarie Gaupp,1 Susanne Engelmann,2 Manuel Liebeke,3 Michael Lalk,3 Michael Hecker,2 and Friedrich Götz1*

Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany,1 Institute for Microbiology, University of Greifswald, 17487 Greifswald, Germany,2 Institute for Pharmaceutical Biology, University of Greifswald, 17487 Greifswald, Germany3

Received 1 July 2008/ Accepted 18 September 2008

Here, we investigate the functionality of the oxygen-responsive nitrogen regulation system NreABC in the human pathogen Staphylococcus aureus and evaluate its role in anaerobic gene regulation and virulence factor expression. Deletion of nreABC resulted in severe impairment of dissimilatory nitrate and nitrite reduction and led to a small-colony phenotype in the presence of nitrate during anaerobic growth. For characterization of the NreABC regulon, comparative DNA microarray and proteomic analyses between the wild type and nreABC mutant were performed under anoxic conditions in the absence and presence of nitrate. A reduced expression of virulence factors was not observed in the mutant. However, both the transcription of genes involved in nitrate and nitrite reduction and the accumulation of corresponding proteins were highly decreased in the nreABC mutant, which was unable to utilize nitrate as a respiratory oxidant and, hence, was forced to use fermentative pathways. These data were corroborated by the quantification of the extracellular metabolites lactate and acetate. Using an Escherichia coli-compatible two-plasmid system, the activation of the promoters of the nitrate and nitrite reductase operons and of the putative nitrate/nitrite transporter gene narK by NreBC was confirmed. Overall, our data indicate that NreABC is very likely a specific regulation system that is essential for the transcriptional activation of genes involved in dissimilatory reduction and transport of nitrate and nitrite. The study underscores the importance of NreABC as a fitness factor for S. aureus in anoxic environments.

* Corresponding author. Mailing address: Mikrobielle Genetik, Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany. Phone: 49 7071 2974636. Fax: 49 7071 295937. E-mail: friedrich.goetz{at}uni-tuebingen.de

{triangledown} Published ahead of print on 26 September 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} S.S. and S.F. contributed equally to this work.

Journal of Bacteriology, December 2008, p. 7847-7858, Vol. 190, No. 23
0021-9193/08/$08.00+0     doi:10.1128/JB.00905-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Somerville, G. A., Proctor, R. A. (2009). At the Crossroads of Bacterial Metabolism and Virulence Factor Synthesis in Staphylococci. Microbiol. Mol. Biol. Rev. 73: 233-248 [Abstract] [Full Text]  


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