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Record W4385394915 · doi:10.1016/j.celrep.2023.112861

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile

2023· article· en· W4385394915 on OpenAlexaff
Qiwen Dong, Huaiying Lin, Marie-Maude Allen, Julian R. Garneau, Jonathan K. Sia, Rita C. Smith, Fidel Haro, Tracy McMillen, Rosemary L. Pope, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Nicholas P. Dylla, Claire E. Kohout, Anitha Sundararajan, Evan S. Snitkin, Vincent B. Young, Louis‐Charles Fortier, Mini Kamboj, Eric G. Pamer

Bibliographic record

VenueCell Reports · 2023
Typearticle
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsUniversité de Sherbrooke
FundersNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Institutes of HealthUniversity of Chicago
KeywordsVirulenceBiologyMicrobiologyClostridium difficile toxin BClostridium difficileClostridium difficile toxin AGeneClostridioidesLocus (genetics)Pathogenicity islandToxinVirologyGenetics

Abstract

fetched live from OpenAlex

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.

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)0.001
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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.280
Threshold uncertainty score0.902

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.043
GPT teacher head0.311
Teacher spread0.268 · 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 designObservational
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

Citations24
Published2023
Admission routes1
Has abstractyes

Explore more

Same venueCell ReportsSame topicClostridium difficile and Clostridium perfringens researchFrench-language works237,207