Redox sensing by a Rex‐family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus |
| |
| Authors: | Martin Pagels Stephan Fuchs Jan Pané‐Farré Christian Kohler Leonhard Menschner Michael Hecker Peter J. McNamarra Mikael C. Bauer Claes Von Wachenfeldt Manuel Liebeke Michael Lalk Gunnar Sander Christof Von Eiff Richard A. Proctor Susanne Engelmann |
| |
| Affiliation: | 1. Institute for Microbiology and;2. Both authors contributed equally.;3. Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA.;4. Departments of Biophysical Chemistry and;5. Biology, Lund University, Lund, Sweden.;6. Institute for Pharmaceutical Biology, University of Greifswald, Greifswald, Germany.;7. Institute for Medical Microbiology, University Hospital Münster, Münster, Germany.;8. Present address: Wyeth Pharma, Münster, Germany. |
| |
| Abstract: | An alignment of upstream regions of anaerobically induced genes in Staphylococcus aureus revealed the presence of an inverted repeat, corresponding to Rex binding sites in Streptomyces coelicolor. Gel shift experiments of selected upstream regions demonstrated that the redox‐sensing regulator Rex of S. aureus binds to this inverted repeat. The binding sequence – TTGTGAAW4TTCACAA – is highly conserved in S. aureus. Rex binding to this sequence leads to the repression of genes located downstream. The binding activity of Rex is enhanced by NAD+ while NADH, which competes with NAD+ for Rex binding, decreases the activity of Rex. The impact of Rex on global protein synthesis and on the activity of fermentation pathways under aerobic and anaerobic conditions was analysed by using a rex‐deficient strain. A direct regulatory effect of Rex on the expression of pathways that lead to anaerobic NAD+ regeneration, such as lactate, formate and ethanol formation, nitrate respiration, and ATP synthesis, is verified. Rex can be considered a central regulator of anaerobic metabolism in S. aureus. Since the activity of lactate dehydrogenase enables S. aureus to resist NO stress and thus the innate immune response, our data suggest that deactivation of Rex is a prerequisite for this phenomenon. |
| |
| Keywords: | |
|
|
