<i>Mycobacterium bovis</i>BCG disrupts the interaction of Rab7 with RILP contributing to inhibition of phagosome maturation
Bibliographic record
Abstract
Phagosomes containing M. tuberculosis and M. bovis BCG interact normally with early endosomes but fail to fuse with late endosomes and lysosomes. Whereas many early events of mycobacterial phagosomes have been elucidated, the exact mechanism of the inhibition of fusion with lysosomes is still unclear. Several Rab GTPase proteins were shown to be involved in membrane fusion and vesicular transport. In particular, Rab7 associates with the phagosomal membrane and regulates the fusion between late endosomes and lysosomes. This function of Rab7 was shown to be mediated in epithelial cell models by the Rab7 effector RILP (Rab7-interacting lysosomal protein). However, the relevance of Rab7-RILP interaction to phagosome biogenesis in macrophage infected with mycobacteria is still unknown. In this study, cotransfection of RAW 264.7 cells with Rab7 and RILP revealed that Rab7-RILP interaction occurs in macrophages ingesting latex beads. Thereafter, this cell system model was used to demonstrate that infection with live but not killed M. bovis BCG inhibited RILP recruitment despite Rab7 acquisition by the phagosome. Further investigation using immobilized RILP to pull down active Rab7 (GTP-bound form) from macrophage lysates demonstrated that inactive Rab7 (GDP-bound form) predominates in cells infected with live BCG. In addition, cell-free system experiments demonstrated that BCG culture supernatant contains a factor that catalyzes the GTP/GDP switch on recombinant Rab7 molecules. Such a factor was shown to diffuse beyond BCG phagosomes and target other Rab7-positive compartments. These findings suggest that live mycobacteria express within the macrophage a Rab7 deactivating factor leading to abortion of RILP-mediated fusion with lysosomes.
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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 | 0.001 | 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".