Eps15, but not AP‐2, is recruited and essential for the formation of enteropathogenic <i>E. coli</i> pedestals
Bibliographic record
Abstract
Enteropathogenic Escherichia coli (EPEC) are extracellular pathogens that cause serious infantile diarrhea. The hallmark of EPEC pathogenesis is its ability to colonize the surface of gut epithelial cells and inject effector proteins to hijack sub‐cellular components, forming characteristic actin‐rich pedestals beneath the attached bacteria. Efficient formation of pedestals requires the phosphorylation of the EPEC effector protein Tir at Tyrosine 474 (Y474). Clathrin, a key component in receptor‐mediated endocytosis, was previously found to participate in pedestal formation. We examined the clathrin‐associated endocytic proteins AP‐2 and its binding partner, Eps15. We found that Eps15 is recruited to the pedestal together with clathrin while AP‐2 is not. Further analysis using GFP‐Eps15 mutants revealed that such recruitment does not require the AP‐2 binding domain at the Eps15 C‐terminus, confirming previous results that pedestal forms efficiently in the absence of AP‐2. RNA interference showed that pedestal formation is inhibited in the absence of Eps15, suggesting Eps15 is required to generate pedestals. Finally we showed that Eps15 recruitment to pedestals required Tir Y474 phosphorylation. These results reveal a novel internalization subversion strategy employed by extracellular pathogens, supporting the recent paradigm that endocytic proteins are important for EPEC‐mediated disease. Grant Funding Source: CIHR
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| 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) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".