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Record W4402846517 · doi:10.1101/2024.09.24.614756

Altered oral microbiota of drug-resistant organism carriers exhibit impaired gram-negative pathogen inhibition

2024· preprint· en· W4402846517 on OpenAlexaff
Susan Zelasko, Mary-Hannah Swaney, Won Se Suh, Shelby Sandstrom, Caitlin M. Carlson, Julian Cagnazzo, Athena E. Golfinos, Jen Fossen, David R. Andes, Lindsay Kalan, Nasia Safdar, Cameron R. Currie

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldDentistry
TopicOral microbiology and periodontitis research
Canadian institutionsMcMaster University
Fundersnot available
KeywordsPathogenMicrobiologyGram-negative bacteriaDrugGramOrganismBiologyDrug resistanceBacteriaPharmacologyEscherichia coliBiochemistryGeneticsGene

Abstract

fetched live from OpenAlex

Abstract The oral microbiome has been understudied as a reservoir for clinical pathogens, including drug-resistant strains. Understanding how alterations in microbiome functioning render this site vulnerable to colonization is essential, as multidrug-resistant organisms (MDRO) carriage is a major risk factor for developing serious infections. To advance our knowledge of oral MDRO carriage and protection against pathogen colonization conferred by native microbiota, we examined microbiomes from individuals colonized by MDROs (n=33) and non-colonized age-matched controls (n=30). Shotgun metagenomic analyses of oral swabs from study participants revealed significant differences in microbial communities with depletion of Streptococcus spp. among those colonized by multidrug-resistant gram-negative bacilli (RGNB), compared to non-carriers. We utilized metagenomic sequencing to characterize the oral resistome and find antimicrobial resistance genes are present in higher abundance among RNGB carriers versus non-carriers. High-throughput co-culture screening revealed oral bacteria isolated from MDRO non-carriers demonstrate greater inhibition of gram-negative pathogens, compared to isolates from carriers. Moreover, biosynthetic gene clusters from streptococci are found in higher abundance from non-carrier microbiomes, compared to RGNB carrier microbiomes. Bioactivity-guided fractionation of extracts from Streptococcus isolate SID2657 demonstrated evidence of strong E. coli and A. baumannii inhibition in a murine model of infection. Together, this provides evidence that oral microbiota shape this dynamic microbial community and may serve as an untapped source for much-needed antimicrobial small-molecules.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.015
GPT teacher head0.247
Teacher spread0.233 · 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 source (direct Gemma or distilled Codex), 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

Citations1
Published2024
Admission routes1
Has abstractyes

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