ArticleNature communications2021
Temporal evolution of master regulator Crp identifies pyrimidines as catabolite modulator factors.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
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- A model industrial workhorse: Bacillus subtilis strain 168 and its genome after a quarter of a century.Microbial biotechnology · 2023Review
- The cAMP receptor protein (CRP) enhances the competitive nature of Salmonella Typhimurium.Archives of microbiology · 2023Article
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- cAMP Activation of the cAMP Receptor Protein, a Model Bacterial Transcription Factor.Journal of microbiology (Seoul, Korea) · 2023Review
- Disrupting the ArcA Regulatory Network Amplifies the Fitness Cost of Tetracycline Resistance in Escherichia coli.mSystems · 2023Article
- Unified Access to Pyrimidines and Quinazolines Enabled by N-N Cleaving Carbon Atom Insertion.Journal of the American Chemical Society · 2022Article
- Inactivation of the Pyrimidine BiosynthesisMicroorganisms · 2022Article
- Missing Links Between Gene Function and Physiology in Genomics.Frontiers in physiology · 2022Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The evolution of microorganisms often involves changes of unclear relevance, such as transient phenotypes and sequential development of multiple adaptive mutations in hotspot genes. Previously, we showed that ageing colonies of an E. coli mutant unable to produce cAMP when grown on maltose, accumulated mutations in the crp gene (encoding a global transcription factor) and in genes involved in pyrimidine metabolism such as cmk; combined mutations in both crp and cmk enabled fermentation of maltose (which usually requires cAMP-mediated Crp activation for catabolic pathway expression). Here, we study the sequential generation of hotspot mutations in those genes, and uncover a regulatory role of pyrimidine nucleosides in carbon catabolism. Cytidine binds to the cytidine regulator CytR, modifies the expression of sigma factor 32 (RpoH), and thereby impacts global gene expression. In addition, cytidine binds and activates a Crp mutant directly, thus modulating catabolic pathway expression, and could be the catabolite modulating factor whose existence was suggested by Jacques Monod and colleagues in 1976. Therefore, transcription factor Crp appears to work in concert with CytR and RpoH, serving a dual role in sensing both carbon availability and metabolic flux towards DNA and RNA. Our findings show how certain alterations in metabolite concentrations (associated with colony ageing and/or due to mutations in metabolic or regulatory genes) can drive the evolution in non-growing cells.
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