ArticlePLoS pathogens2024
A conserved switch controls virulence, sporulation, and motility in C. difficile.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Distinctive spore architecture and developmental biology ofJournal of bacteriology · 2026Article
- Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026Review
- Deciphering strain differences in codY regulation ofMicrobiology spectrum · 2026Article
- Characterization of a hypersporulating strain derivativebioRxiv : the preprint server for biology · 2025Article
- The Pxp Complex Detoxifies 5-Oxoproline and Promotes the Growth of Clostridioides difficile.Molecular microbiology · 2025Article
- A metabolite dehydrogenase pathway represses sporulation of Clostridioides difficile.Anaerobe · 2025Article
- Regulatory networks: Linking toxin production and sporulation in Clostridioides difficile.Anaerobe · 2025Review
- Review
- The RgaS-RgaR two-component system promotesbioRxiv : the preprint server for biology · 2023Article
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Authors and funding
8 authors.
Funding
Abstract
Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile. In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that directly regulate C. difficile Spo0A activity are not defined. In the well-studied Bacillus species, Spo0A is directly inactivated by Spo0E, a small phosphatase. To understand Spo0E function in C. difficile, we created a null mutation of the spo0E ortholog and assessed sporulation and physiology. The spo0E mutant produced significantly more spores, demonstrating Spo0E represses C. difficile sporulation. Unexpectedly, the spo0E mutant also exhibited increased motility and toxin production, and enhanced virulence in animal infections. We uncovered that Spo0E interacts with both Spo0A and the toxin and motility regulator, RstA. Direct interactions between Spo0A, Spo0E, and RstA constitute a previously unknown molecular switch that coordinates sporulation with motility and toxin production. Reinvestigation of Spo0E function in B. subtilis revealed that Spo0E induced motility, demonstrating Spo0E regulation of motility and sporulation among divergent species. Further, 3D structural analyses of Spo0E revealed specific and exclusive interactions between Spo0E and binding partners in C. difficile and B. subtilis that provide insight into the conservation of this regulatory mechanism among different species.
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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.