ArticlePLoS pathogens2022
Coordinated modulation of multiple processes through phase variation of a c-di-GMP phosphodiesterase in Clostridioides difficile.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- A programmed reset mechanism primesScience advances · 2026Article
- Phase variable colony morphotypes ofInfection and immunity · 2026Article
- Phylogenomic analysis of the collagen-like BclA proteins inApplied and environmental microbiology · 2026Article
- Article
- Phase variable colony morphotypes ofbioRxiv : the preprint server for biology · 2026Article
- Characterization of a hypersporulating strain derivativebioRxiv : the preprint server for biology · 2025Article
- Phase variation of Clostridioides difficile colony morphology occurs via modulation of cell division.PLoS pathogens · 2025Article
- Article
- Regulatory networks: Linking toxin production and sporulation in Clostridioides difficile.Anaerobe · 2025Review
- 100+ years of phase variation: the premier bacterial bet-hedging phenomenon.Microbiology (Reading, England) · 2025Review
- Allele-linked divergence in SlpA and TcdB drives distinct immune and cytotoxic responses that distinguish ST01 from non-ST01 strains in Clade 2 Clostridioides difficile.Access microbiology · 2025Article
- The conserved noncoding RNA ModT coordinates growth and virulence in Clostridioides difficile.PLoS biology · 2024Article
- Article
- Phase Variation of Flagella and Toxins in Clostridioides difficile is Mediated by Selective Rho-dependent Termination.Journal of molecular biology · 2024Article
- An intact S-layer is advantageous to Clostridioides difficile within the host.PLoS pathogens · 2023Article
- Evolution of cyclic di-GMP signalling on a short and long term time scale.Microbiology (Reading, England) · 2023Article
- Article
- Recent advances and perspectives in nucleotide second messenger signaling in bacteria.microLife · 2023Review
- Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The opportunistic nosocomial pathogen Clostridioides difficile exhibits phenotypic heterogeneity through phase variation, a stochastic, reversible process that modulates expression. In C. difficile, multiple sequences in the genome undergo inversion through site-specific recombination. Two such loci lie upstream of pdcB and pdcC, which encode phosphodiesterases (PDEs) that degrade the signaling molecule c-di-GMP. Numerous phenotypes are influenced by c-di-GMP in C. difficile including cell and colony morphology, motility, colonization, and virulence. In this study, we aimed to assess whether PdcB phase varies, identify the mechanism of regulation, and determine the effects on intracellular c-di-GMP levels and regulated phenotypes. We found that expression of pdcB is heterogeneous and the orientation of the invertible sequence, or 'pdcB switch', determines expression. The pdcB switch contains a promoter that when properly oriented promotes pdcB expression. Expression is augmented by an additional promoter upstream of the pdcB switch. Mutation of nucleotides at the site of recombination resulted in phase-locked strains with significant differences in pdcB expression. Characterization of these mutants showed that the pdcB locked-ON mutant has reduced intracellular c-di-GMP compared to the locked-OFF mutant, consistent with increased and decreased PdcB activity, respectively. These alterations in c-di-GMP had concomitant effects on multiple known c-di-GMP regulated processes, indicating that phase variation of PdcB allows C. difficile to coordinately diversify multiple phenotypes in the population to enhance survival.
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