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 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".