Cyclophilin A is Crucial for <i>Listeria</i> and <i>Salmonella</i> Invasion and Cell‐to‐Cell Spreading
Bibliographic record
Abstract
The actin cytoskeleton is a common target for a variety of pathogens. Listeria monocytogenes ( Listeria ) bacteria control the actin polymerization machinery within eukaryotic cells for their entry, intracellular motility and subsequent spreading from one cell to another. These microbes use actin‐rich structures called comet tails to generate protrusions at the plasma membrane (referred to as listeriopods) for cell‐to‐cell spreading. Unfortunately, the precise molecular mechanisms governing this process remain elusive. Another actin‐hijacking bacterial pathogen is Salmonella typhimurium ( Salmonella ). These bacteria exploit actin‐based membrane ruffling in order to enter cells. Although actin regulators have been linked to this process, a thorough understanding of the molecular constituents and their functions at these structures has not yet been investigated. We have previously shown that the peptidyl prolyl cis‐trans isomerase (PPIase), cyclophilin A (CypA), a cytosolic protein involved in protein folding, is recruited to actin‐rich structures generated by Listeria . Here we expanded on our previous discovery and tested the hypothesis that CypA is important for the pathogenesis of Listeria . Infections of murine fibroblasts depleted of CypA revealed that listeriopods were structurally collapsed, suggesting a unique role of cellular PPIases during cell‐to‐cell spreading of Listeria . Importantly, when CypA was reexpressed in these cells, listeriopods appeared normal. Curiously, cytoplasmic comet tails remained morphologically unchanged when CypA was absent. We also found that CypA is recruited to actin‐rich membrane ruffles generated by Salmonella during its entry into cells. Surprisingly, invasion assays of murine fibroblasts showed that invasion by Listeria and Salmonella increases significantly in cells knocked‐out for CypA. These results suggest a novel membrane‐associated mechanism whereby CypA regulates the efficiency of invasion and cell‐to‐cell transmission of bacteria. Support or Funding Information Grant Funding Source: NSERC and departmental funds
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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".