AEM Accepts, published online ahead of print on 30 October 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Baker, J. Articles by Morrissey, J. A. PubMed PubMed Citation Articles by Baker, J. Articles by Morrissey, J. A. Agricola Articles by Baker, J. Articles by Morrissey, J. A.

 Previous Article  |  Next Article 

Appl. Environ. Microbiol. doi:10.1128/AEM.02268-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Copper stress induces a global stress response and represses sae and agr expression and biofilm formation in Staphylococcus aureus.

Jonathan Baker, Sutthirat Sitthisak, Mrittika Sengupta, Miranda Johnson, R. K. Jayaswal, and Julie A. Morrissey^*

Dept. of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK; Department of Biological Sciences, Illinois State University, Normal, IL 61790, USA

^* To whom correspondence should be addressed. Email: jam26{at}le.ac.uk.

Copper is an important co-factor for many enzymes, however high levels of copper are toxic. Therefore bacteria must ensure there is sufficient copper for use as a co-factor but more importantly must limit free intracellular levels to prevent toxicity. In this study we have used DNA microarray to identify S. aureus copper responsive genes. Transcriptional profiling of S. aureus SH1000 grown in excess copper identified a number of genes which fall into four groups suggesting that S. aureus has four main mechanisms for adapting to high levels of environmental copper. (i) Induction of direct copper homeostasis mechanisms, (ii) increased oxidative stress resistance, (iii) expression of the misfolded protein response, and (iv) repression of a number of transporters and global regulators such as Agr and Sae. Our experimental data confirms that resistance to oxidative stress and particularly H₂O₂ scavenging is an important S. aureus copper resistance mechanism. Our previous studies have demonstrated that Eap and Emp proteins, which are positively regulated by Agr and Sae, are required for biofilm formation in low iron growth conditions. Our transcriptional analysis has confirmed that sae, agr and eap are repressed in high copper and that biofilm formation is indeed repressed by high copper. Therefore our results may provide an explanation of how copper films can prevent biofilm formation on catheters.