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Record W3009078156 · doi:10.1073/pnas.1916965117

Intestinal bile acids directly modulate the structure and function of <i>C. difficile</i> TcdB toxin

2020· article· en· W3009078156 on OpenAlexafffund
John Tam, Simoun Icho, Evelyn Utama, Kathleen E. Orrell, Rodolfo F. Gómez‐Biagi, Casey M. Theriot, Heather K. Kroh, Stacey A. Rutherford, D. Borden Lacy, Roman A. Melnyk

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2020
Typearticle
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsSickKids FoundationUniversity of TorontoHospital for Sick Children
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of General Medical SciencesGovernment of CanadaNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchU.S. Department of Veterans Affairs
KeywordsBile acidToxinOligopeptideClostridium difficile toxin AChemistryAmino acidReceptorBiochemistryBiologyPeptideClostridium difficile

Abstract

fetched live from OpenAlex

Significance Clostridioides difficile is a bacterial pathogen of global importance that is a major cause of hospital-acquired diarrhea. Antibiotic-mediated disruptions to the gut microbiota and associated metabolome promote C. difficile growth and infection through mechanisms that are poorly understood. Here, we show that intestinal bile acids, which are known to play a role in C. difficile germination and outgrowth, also directly bind and inhibit TcdB toxin, the primary virulence determinant of C. difficile . Bile acid binding induces a major conformational change in TcdB structure that prevents receptor binding and uptake into cells. In addition to suggesting a role for bile acids in protecting against C. difficile pathogenesis, these findings highlight an approach to block C. difficile virulence.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.041
Threshold uncertainty score0.346

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.044
GPT teacher head0.300
Teacher spread0.257 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations82
Published2020
Admission routes2
Has abstractyes

Explore more

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