Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis
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The stringent response in Bacillus subtilis was characterized by using proteome and transcriptome approaches. Comparison of protein synthesis patterns of wild-type and relA mutant cells cultivated under conditions which provoke the stringent response revealed significant differences. According to their altered synthesis patterns in response to dl-norvaline, proteins were assigned to four distinct classes: (i) negative stringent control, i.e., strongly decreased protein synthesis in the wild type but not in the relA mutant (e.g., r-proteins); (ii) positive stringent control, i.e., induction of protein synthesis in the wild type only (e.g., YvyD and LeuD); (iii) proteins that were induced independently of RelA (e.g., YjcI); and (iv) proteins downregulated independently of RelA (e.g., glycolytic enzymes). Transcriptome studies based on DNA macroarray techniques were used to complement the proteome data, resulting in comparable induction and repression patterns of almost all corresponding genes. However, a comparison of both approaches revealed that only a subset of RelA-dependent genes or proteins was detectable by proteomics, demonstrating that the transcriptome approach allows a more comprehensive global gene expression profile analysis. The present study presents the first comprehensive description of the stringent response of a bacterial species and an almost complete map of protein-encoding genes affected by (p)ppGpp. The negative stringent control concerns reactions typical of growth and reproduction (ribosome synthesis, DNA synthesis, cell wall synthesis, etc.). Negatively controlled unknown y-genes may also code for proteins with a specific function during growth and reproduction (e.g., YlaG). On the other hand, many genes are induced in a RelA-dependent manner, including genes coding for already-known and as-yet-unknown proteins. A passive model is preferred to explain this positive control relying on the redistribution of the RNA polymerase under the influence of (p)ppGpp.
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In B. subtilis, ylbN has been observed to be downregulated by the stringent response.
“Previously, in B. subtilis,77ylbN has been observed to be downregulated by the stringent response (for example, by the alarmone metabolite ppGpp that is synthesized by a gene present in JCVI-syn3A relA/041478), whereby a cell reduces its growth activity to conserve energy often by decreasing the generation of ribosomes.79”
From Toward the Complete Functional Characterization of a Minimal Bacterial Proteome (2022) · cites this paper as [78]
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Self-citation
- Authors
- Eymann, C., Homuth, G., Scharf, C., & Hecker, M.
- Affiliations
- Universität Greifswald (DE)
- Corresponding author
- Hecker, Michael
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2002-05
- Volume
- 184
- Issue
- 9
- Pages
- 2500-2520
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC134987
- OpenAlex
- W2161630640
- Cited by
- 306
- References
- 96
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 16 · 2019: 2 · 2018: 9 · 2017: 12 · 2016: 5 · 2015: 9 · 2014: 12 · 2013: 7 · 2012: 12
- FWCI
- 12.77
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds der Chemischen Industrie
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Keywords
- stringent response, Bacillus subtilis, RelA, (p)ppGpp, protein synthesis regulation, transcriptome, proteome, gene expression profiling, ribosome biogenesis, glycolytic enzymes
- MeSH terms
- Bacillus subtilis, Bacterial Proteins, Guanosine Tetraphosphate, Ligases, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Valine, Electrophoresis, Gel, Two-Dimensional, Gene Expression, Gene Expression Regulation, Bacterial, DNA, Complementary, Regulon, Oligonucleotide Array Sequence Analysis, Proteome
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