Spx-dependent global transcriptional control is induced by thiol-specific oxidative stress in Bacillus subtilis.
The Spx protein of Bacillus subtilis represses activator-stimulated transcription by interacting with the C-terminal domain of RNA polymerase (RNAP) alpha subunit. Its concentration increases in cells lacking the ATP-dependent protease, ClpXP, resulting in severe effects on growth and developmental processes. Microarray analysis was undertaken to identify genes that are induced or repressed when Spx interacts with RNAP. The induced genes included those encoding products known to function in maintaining thiol homeostasis. Two genes, thioredoxin (trxA) and thioredoxin reductase (trxB), are transcriptionally induced under conditions of thiol-specific oxidative (disulfide) stress by a mechanism involving Spx-RNAP interaction. Disulfide stress also results in an increase in Spx-dependent transcriptional repression. The increase in Spx activity in cells encountering disulfide stress is due in part to a posttranscriptional mechanism of spx control resulting in an increase in Spx concentration. An spx null mutant and a strain bearing an allele of rpoA that prevents Spx-RNAP interaction show hypersensitivity to disulfide stress. From these results, it is proposed that Spx is an activator that mobilizes the operations necessary to reverse the effects of oxidative damage, but it also serves as a negative regulator that causes the postponement of developmental programs and energy-consuming growth-related functions while the cell copes with the period of stress.
Nakano
Shunji
S
Department of Environmental and Biomolecular Systems, OGI School of Science and Engineering, Oregon Health and Science University, Beaverton, OR 97006, USA.
Küster-Schöck
Elke
E
Grossman
Alan D
AD
Zuber
Peter
P
D000483:Alleles; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000378:metabolism*; D015153:Blotting, Western; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004220:Disulfides; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004220:Disulfides; D012333:RNA, Messenger; D012097:Repressor Proteins; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D012321:DNA-Directed RNA Polymerases