Redox sensing by a Rex-family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus.
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--TTGTGAAW(4)TTCACAA--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.
Pagels
Martin
M
Institute for Microbiology, University of Greifswald, Greifswald, Germany.
Fuchs
Stephan
S
Pané-Farré
Jan
J
Kohler
Christian
C
Menschner
Leonhard
L
Hecker
Michael
M
McNamarra
Peter J
PJ
Bauer
Mikael C
MC
von Wachenfeldt
Claes
C
Liebeke
Manuel
M
Lalk
Michael
M
Sander
Gunnar
G
von Eiff
Christof
C
Proctor
Richard A
RA
Engelmann
Susanne
S
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D019069:Cell Respiration / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D012097:Repressor Proteins; D009243:NAD