ArticlePLoS pathogens2018
Pleiotropic roles of Clostridium difficile sin locus.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 57 citations in OpenAlex.
- CenIR, an essential BlaIR-family regulatory system inJournal of bacteriology · 2026Article
- Naturally Occurring CodY Variants Alter Ligand Binding, DNA Target Affinity, and Virulence in Clostridioides difficile.Molecular microbiology · 2026Article
- CenIR, an essential BlaIR-family regulatory system inbioRxiv : the preprint server for biology · 2026Article
- Bile acid dependent attenuation of toxin mediated disease is independent of colonization resistance againstbioRxiv : the preprint server for biology · 2026Article
- Deciphering strain differences in codY regulation ofMicrobiology spectrum · 2026Article
- Engineering a PhrC-RapC-SinR quorum sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis in Bacillus subtilis.Microbial cell factories · 2025Article
- Regulatory networks: Linking toxin production and sporulation in Clostridioides difficile.Anaerobe · 2025Review
- Antimicrobial Resistance and New Antimicrobial Agents, A Review of the Literature.Current medicinal chemistry · 2025Review
- The conserved noncoding RNA ModT coordinates growth and virulence in Clostridioides difficile.PLoS biology · 2024Article
- Role of glycogen metabolism inmSphere · 2024Article
- Fight or flee, a vital choice formLife · 2024Article
- Review
- Clostridioides difficile Sporulation.Advances in experimental medicine and biology · 2024Review
- Review
- Host Sorbitol and Bacterial Sorbitol Utilization Promote Clostridioides difficile Infection in Inflammatory Bowel Disease.Gastroenterology · 2023Article
- Regulatory Role of Anti-Sigma Factor RsbW in Clostridioides difficile Stress Response, Persistence, and Infection.Journal of bacteriology · 2023Article
- The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile.NPJ biofilms and microbiomes · 2023Article
- Regulatory transcription factors ofCritical reviews in microbiology · 2023Review
- Response Regulator CD1688 Is a Negative Modulator of Sporulation in Clostridioides difficile.Journal of bacteriology · 2022Article
- Capturing the environment of the Clostridioides difficile infection cycle.Nature reviews. Gastroenterology & hepatology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression. The C. difficile genome carries two sinR homologs in the operon that we named sinR and sinR', coding for SinR (112 aa) and SinR' (105 aa), respectively. In this study, we constructed and characterized sin locus mutants in two different C. difficile strains R20291 and JIR8094, to decipher the locus's role in C. difficile physiology. Transcriptome analysis of the sinRR' mutants revealed their pleiotropic roles in controlling several pathways including sporulation, toxin production, and motility in C. difficile. Through various genetic and biochemical experiments, we have shown that SinR can regulate transcription of key regulators in these pathways, which includes sigD, spo0A, and codY. We have found that SinR' acts as an antagonist to SinR by blocking its repressor activity. Using a hamster model, we have also demonstrated that the sin locus is needed for successful C. difficile infection. This study reveals the sin locus as a central link that connects the gene regulatory networks of sporulation, toxin production, and motility; three key pathways that are important for C. difficile pathogenesis.
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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.