ArticlePLoS genetics2019
The CspC pseudoprotease regulates germination of Clostridioides difficile spores in response to multiple environmental signals.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 28 citations in OpenAlex.
- Structure of core assembly of the Clostridioides difficile germinosome.Nature communications · 2026Article
- Article
- Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026Review
- Advances in understanding the Clostridial spore inner membrane.Archives of microbiology · 2026Review
- The CspC:CspA heterodimer transduces germinant and co-germinant signals during Clostridioides difficile spore germination.PLoS biology · 2026Article
- Phenotypic analysis of variousApplied and environmental microbiology · 2025Article
- Review
- Reactions of SleC, Its Structure and Inhibition in Mitigation of Spore Germination inJournal of the American Chemical Society · 2025Article
- Bile acids as germinants for Clostridioides difficile spores, evidence of adaptation to the gut?FEMS microbiology reviews · 2025Review
- Phenotypic analysis of variousbioRxiv : the preprint server for biology · 2025Article
- Protection against Clostridioides difficile disease by a naturally avirulent strain.Cell host & microbe · 2025Article
- The Impact of YabG Mutations on Clostridioides difficile Spore Germination and Processing of Spore Substrates.Molecular microbiology · 2024Article
- Clostridium septicum manifests a bile salt germinant response mediated by Clostridioides difficile csp gene orthologs.Communications biology · 2024Article
- The impact of YabG mutations onbioRxiv : the preprint server for biology · 2024Article
- Protection againstbioRxiv : the preprint server for biology · 2024Article
- Article
- Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA).The Journal of antibiotics · 2023Article
- A dual-action antibiotic that killsProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Non-ToxigenicAntibiotics (Basel, Switzerland) · 2023Article
- Non-Toxin-BasedPathogens (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The gastrointestinal pathogen, Clostridioides difficile, initiates infection when its metabolically dormant spore form germinates in the mammalian gut. While most spore-forming bacteria use transmembrane germinant receptors to sense nutrient germinants, C. difficile is thought to use the soluble pseudoprotease, CspC, to detect bile acid germinants. To gain insight into CspC's unique mechanism of action, we solved its crystal structure. Guided by this structure, we identified CspC mutations that confer either hypo- or hyper-sensitivity to bile acid germinant. Surprisingly, hyper-sensitive CspC variants exhibited bile acid-independent germination as well as increased sensitivity to amino acid and/or calcium co-germinants. Since mutations in specific residues altered CspC's responsiveness to these different signals, CspC plays a critical role in regulating C. difficile spore germination in response to multiple environmental signals. Taken together, these studies implicate CspC as being intimately involved in the detection of distinct classes of co-germinants in addition to bile acids and thus raises the possibility that CspC functions as a signaling node rather than a ligand-binding receptor.
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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.