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Journal of Bacteriology, November 2007, p. 7911-7919, Vol. 189, No. 21
0021-9193/07/$08.00+0     doi:10.1128/JB.00598-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Staphylococcal Biofilm Formation by Nitrite{triangledown} ,{dagger}

Steffen Schlag,1 Christiane Nerz,1 Timo A. Birkenstock,1 Florian Altenberend,2 and Friedrich Götz1*

Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany,1 Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany2

Received 18 April 2007/ Accepted 17 August 2007

Several environmental stresses have been demonstrated to increase polysaccharide intercellular adhesin (PIA) synthesis and biofilm formation by the human pathogens Staphylococcus aureus and Staphylococcus epidermidis. In this study we characterized an adaptive response of S. aureus SA113 to nitrite-induced stress and show that it involves concomitant impairment of PIA synthesis and biofilm formation. Transcriptional analysis provided evidence that nitrite, either as the endogenous product of respiratory nitrate reduction or after external addition, causes repression of the icaADBC gene cluster, mediated likely by IcaR. Comparative microarray analysis revealed a global change in gene expression during growth in the presence of 5 mM sodium nitrite and indicated a response to oxidative and nitrosative stress. Many nitrite-induced genes are involved in DNA repair, detoxification of reactive oxygen and nitrogen species, and iron homeostasis. Moreover, preformed biofilms could be eradicated by the addition of nitrite, likely the result of the formation of toxic acidified nitrite derivatives. Nitrite-mediated inhibition of S. aureus biofilm formation was abrogated by the addition of nitric oxide (NO) scavengers, suggesting that NO is directly or indirectly involved. Nitrite also repressed biofilm formation of S. epidermidis RP62A.

* 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 24 August 2007.

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

Journal of Bacteriology, November 2007, p. 7911-7919, Vol. 189, No. 21
0021-9193/07/$08.00+0     doi:10.1128/JB.00598-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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