ArticleJournal of bacteriology2006
Analysis of proline reduction in the nosocomial pathogen Clostridium difficile.
Article in Journal of bacteriology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
75 citing papers in PubMed, 123 citations in OpenAlex.
- Mechanisms by which proline reductase ofmBio · 2026Article
- Article
- Recent advances in exploring the composition and evolution of the prokaryotic selenoproteome.Applied and environmental microbiology · 2026Review
- The Pxp Complex Detoxifies 5-Oxoproline and Promotes the Growth of Clostridioides difficile.Molecular microbiology · 2025Article
- Caffeic acid phenethyl ester protectseLife · 2025Article
- A metabolite dehydrogenase pathway represses sporulation of Clostridioides difficile.Anaerobe · 2025Article
- Iron-sulfur cluster-dependent enzymes and molybdenum-dependent reductases in the anaerobic metabolism of human gut microbes.Metallomics : integrated biometal science · 2024Review
- Identification of avaC from Human Gut Microbial Isolates that Converts 5AVA to 2-Piperidone.Journal of microbiology (Seoul, Korea) · 2024Article
- Glycine fermentation byInfection and immunity · 2023Article
- Inhibition of selenoprotein synthesis is not the mechanism by which auranofin inhibits growth of Clostridioides difficile.Scientific reports · 2023Article
- The Novel DNA Binding Mechanism of Ridinilazole, a PrecisionAntimicrobial agents and chemotherapy · 2023Article
- Elucidating dynamic anaerobe metabolism with HRMASNature chemical biology · 2023Article
- Eight Unexpected Selenoprotein Families in Organometallic Biochemistry in Clostridium difficile, in ABC Transport, and in Methylmercury Biosynthesis.Journal of bacteriology · 2023Article
- Article
- Characterizing metabolic drivers ofFrontiers in pharmacology · 2023Article
- Food for thought-The link between Clostridioides difficile metabolism and pathogenesis.PLoS pathogens · 2023Review
- Article
- d-Proline Reductase Underlies Proline-Dependent Growth of Clostridioides difficile.Journal of bacteriology · 2022Article
- Reconsidering the in vivo functions of Clostridial Stickland amino acid fermentations.Anaerobe · 2022Review
- Clostridium sporogenes uses reductive Stickland metabolism in the gut to generate ATP and produce circulating metabolites.Nature microbiology · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clostridium difficile, a proteolytic strict anaerobe, has emerged as a clinically significant nosocomial pathogen in recent years. Pathogenesis is due to the production of lethal toxins, A and B, members of the large clostridial cytotoxin family. Although it has been established that alterations in the amino acid content of the growth medium affect toxin production, the molecular mechanism for this observed effect is not yet known. Since there is a paucity of information on the amino acid fermentation pathways used by this pathogen, we investigated whether Stickland reactions might be at the heart of its bioenergetic pathways. Growth of C. difficile on Stickland pairs yielded large increases in cell density in a limiting basal medium, demonstrating that these reactions are tied to ATP production. Selenium supplementation was required for this increase in cell yield. Analysis of genome sequence data reveals genes encoding the protein components of two key selenoenzyme reductases, glycine reductase and d-proline reductase (PR). These selenoenzymes were expressed upon the addition of the corresponding Stickland acceptor (glycine, proline, or hydroxyproline). Purification of the selenoenzyme d-proline reductase revealed a mixed complex of PrdA and PrdB (SeCys-containing) proteins. PR utilized only d-proline but not l-hydroxyproline, even in the presence of an expressed and purified proline racemase. PR was found to be independent of divalent cations, and zinc was a potent inhibitor of PR. These results show that Stickland reactions are key to the growth of C. difficile and that the mechanism of PR may differ significantly from that of previously studied PR from nonpathogenic species.
Indexed as
Identifiers
What OpenQuestion holds
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.