Étude moléculaire de l'interaction entre les bactériophages de Clostridioides difficile et leur récepteur cellulaire, la protéine de surface SlpA
Bibliographic record
Abstract
The emergence of hypervirulent strains of Clostridioides difficile, a leading cause of nosocomial infections in industrialized countries, underscores the urgent need for new therapeutic strategies. Among them, phage therapy, which relies on the use of bacteriophages specifically targeting bacteria, has regained interest. However, its application against C. difficile remains limited by our incomplete understanding of the molecular mechanisms involved in host recognition by phages. This thesis aimed to elucidate the molecular basis of the interaction between C. difficile-infecting phages and their principal receptor identified to date, the surface layer protein SlpA, the major component of the S- layer. In a first study, using the epidemic strain R20291 and its derivative FM2.5, a natural mutant lacking slpA, we demonstrated that the absence of SlpA confers complete resistance to several phages, and that sensitivity can be restored by reintroducing slpA via a plasmid. Furthermore, complementation of FM2.5 with 12 different slpA isoforms revealed a high specificity of interaction between isoforms and the tested phages. In the second part, we identified the regions of this receptor critical for phage recognition. SlpA is cleaved into two fragments: a high- molecular-weight (HMW) subunit anchored to the cell surface and a low-molecular-weight (LMW) subunit exposed externally, itself divided into two domains, D1 and D2. We generated targeted bacterial mutants, including complete and partial deletions of domain D2, chimeric constructs between isoforms, and variants expressing only the HMW fragment. Infection and adsorption assays highlighted a key role of domain D2 in recognition by certain phages. Chimeras further showed that efficient interaction generally requires the isoform- specific combination of both fragments, suggesting recognition based on fine structural determinants unique to each isoform. Overall, this work improves our mechanistic understanding of phage–SlpA interactions in C. difficile and, more broadly, of phage–S-layer interactions. It paves the way for the design of broad-spectrum phage cocktails and recombinant phages targeting refractory strains, to develop personalized therapies against recurrent C. difficile infections.
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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) | 0.000 | 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 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".