ArticleNucleic acids research2012
Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.
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Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.
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- CcpA-mediated regulation of cellular energy metabolism in the ruminal bacteriumMicrobiology spectrum · 2025Article
- Proline Stickland fermentation supportsApplied and environmental microbiology · 2025Article
- The Pxp Complex Detoxifies 5-Oxoproline and Promotes the Growth of Clostridioides difficile.Molecular microbiology · 2025Article
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- A metabolite dehydrogenase pathway represses sporulation of Clostridioides difficile.Anaerobe · 2025Article
- Regulatory networks: Linking toxin production and sporulation in Clostridioides difficile.Anaerobe · 2025Review
- Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbeProceedings of the National Academy of Sciences of the United States of America · 2025Article
- In-depth characterization of accessory gene regulator loci and associated virulence factors inCurrent research in microbial sciences · 2025Article
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- Characterization ofMicroorganisms · 2024Article
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- Environmental and Nutritional Parameters Modulating Genetic Expression for Virulence Factors ofAntibiotics (Basel, Switzerland) · 2024Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
The catabolite control protein CcpA is a pleiotropic regulator that mediates the global transcriptional response to rapidly catabolizable carbohydrates, like glucose in Gram-positive bacteria. By whole transcriptome analyses, we characterized glucose-dependent and CcpA-dependent gene regulation in Clostridium difficile. About 18% of all C. difficile genes are regulated by glucose, for which 50% depend on CcpA for regulation. The CcpA regulon comprises genes involved in sugar uptake, fermentation and amino acids metabolism, confirming the role of CcpA as a link between carbon and nitrogen pathways. Using combination of chromatin immunoprecipitation and genome sequence analysis, we detected 55 CcpA binding sites corresponding to ∼140 genes directly controlled by CcpA. We defined the C. difficile CcpA consensus binding site (cre(CD) motif), that is, 'RRGAAAANGTTTTCWW'. Binding of purified CcpA protein to 19 target cre(CD) sites was demonstrated by electrophoretic mobility shift assay. CcpA also directly represses key factors in early steps of sporulation (Spo0A and SigF). Furthermore, the C. difficile toxin genes (tcdA and tcdB) and their regulators (tcdR and tcdC) are direct CcpA targets. Finally, CcpA controls a complex and extended regulatory network through the modulation of a large set of regulators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.