Intimate attachment of A/E pathogens disrupt Tight Junctions <i>in vivo</i>
Bibliographic record
Abstract
The attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) cause serious disease in humans resulting in profuse diarrhea and occasional death. These pathogens attach to the surfaces of intestinal epithelial cells and use a type‐three secretion system (TTSS) to inject effector proteins which collapse (efface) the microvilli of the host cells and hijack normal host cellular processes. In vitro (cell culture) work has demonstrated that tight junctions (TJs) are one of the structures targeted by these pathogens. In order to test whether TJs are disrupted in vivo , the A/E pathogen, Citrobacter rodentium (CR) , was used to infect mice as a small animal model. CR contains the major pathogenic effector proteins found in all A/E pathogens and colonizes the colon at high levels. Following infection, the TJ proteins claudins‐1, ‐3 and ‐5 are redistributed from the cell membrane to the cell cytoplasm. In addition, molecular tracers injected into the lumen of murine colons following 7‐day infection by wild‐type (WT) CR penetrate the epithelium. These effects are dependent on the effector protein EspF but not Map. Morphologically, TJ regions appear smaller following WT CR infection when compared with TTSS or espF mutant bacterial infections. The effects on TJs require the intimate attachment of the bacteria to the host cells. Bacterially induced inflammation does not affect the localization of claudins‐1, ‐3 or ‐5. This work was funded by the following agencies: HHMI, CAG/Aztra Zeneca/CIHR, MSFHR and The Killam Foundation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".