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Record W3134015568 · doi:10.1038/s41467-021-21718-y

Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation

2021· article· en· W3134015568 on OpenAlex
Kira L. Tomlinson, Tania Wong Fok Lung, Felix Dach, Medini K. Annavajhala, Stanislaw J. Gabryszewski, Ryan A. Groves, Marija Drikic, Nancy Francoeur, Shwetha Hara Sridhar, Melissa Smith, Sara Khanal, Clemente J. Britto, Robert Sebra, Ian A. Lewis, Anne‐Catrin Uhlemann, Barbara C. Kahl, Alice Prince, Sebastián A. Riquelme

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicAntimicrobial Resistance in Staphylococcus
Canadian institutionsUniversity of Calgary
FundersNational Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesGeorgia Clinical and Translational Science AllianceWeill Cornell Medical CollegeNational Center for Research ResourcesNational Institute of General Medical SciencesNational Heart, Lung, and Blood InstituteNational Institutes of HealthU.S. Department of Health and Human ServicesVertex PharmaceuticalsCystic Fibrosis FoundationDeutsche Forschungsgemeinschaft
KeywordsBiofilmStaphylococcus aureusMicrobiologyGlycolysisBacteriaImmune systemBiologyPathogenHuman pathogenExtracellularMetaboliteStaphylococcal infectionsChemistryEnzymeBiochemistryImmunology

Abstract

fetched live from OpenAlex

Staphylococcus aureus is a prominent human pathogen that readily adapts to host immune defenses. Here, we show that, in contrast to Gram-negative pathogens, S. aureus induces a distinct airway immunometabolic response dominated by the release of the electrophilic metabolite, itaconate. The itaconate synthetic enzyme, IRG1, is activated by host mitochondrial stress, which is induced by staphylococcal glycolysis. Itaconate inhibits S. aureus glycolysis and selects for strains that re-direct carbon flux to fuel extracellular polysaccharide (EPS) synthesis and biofilm formation. Itaconate-adapted strains, as illustrated by S. aureus isolates from chronic airway infection, exhibit decreased glycolytic activity, high EPS production, and proficient biofilm formation even before itaconate stimulation. S. aureus thus adapts to the itaconate-dominated immunometabolic response by producing biofilms, which are associated with chronic infection of the human airway.

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.

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 categoriesMeta-epidemiology (narrow)
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 score0.556
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0010.002
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 head0.030
GPT teacher head0.328
Teacher spread0.298 · 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