Francisella enters host cells by Clathrin‐mediated endocytosis at a cholesterol rich domain
Bibliographic record
Abstract
Francisella tularensis are highly infectious bacterial pathogens that cause a type of acute debilitating febrile illness called tularemia. While Francisella reportedly colonize and establish infection in multiple organs, the liver remains as the primary site of infections. Although these infections are responsible for the mortality of 35% of infected individuals if left untreated, the strategies these pathogens use to invade non‐phagocytic cells remain elusive. Therefore, our objective is to examine the subcellular mechanisms these bacteria utilize to infect their hosts. We generated the hypothesis that Francisella co‐opt normal human endocytic machinery to internalize into host epithelial cells. To test this, we developed two in vitro Francisella‐ based infection models using murine hepatocyte epithelial cells. By using a combination of pharmacological inhibitors, RNA interference‐mediated protein knock down and protein immunolocalization, we showed that Francisella exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We conclude that this is the first study demonstrating the importance and significance of clathrin‐mediated endocytosis to facilitate efficient Francisella invasion into non‐phagocytic cells. 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) | 0.001 | 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".