Structural determinants of SlpA-mediated phage recognition in Clostridioides difficile
Bibliographic record
Abstract
Phage therapy is a promising alternative to antibiotics for treating Clostridioides difficile infections. Despite its fundamental importance, the initial and most critical step of C. difficile phage infection cycle - the precise recognition of a host receptor - remains poorly understood. The surface-layer protein SlpA was previously identified as a general phage receptor in C. difficile, but the molecular determinants of phage-S-layer interactions remain unclear. We investigated the structural features of SlpA required for phage recognition by engineering and expressing modified isoforms in FM2.5 and R20291 ΔslpA strains. By deleting specific SlpA domains and creating chimeric constructs from different isoforms, we assessed the capacity of seven phages to adsorb and infect the complemented strains. Our results demonstrate that both the LMW and HMW fragments of the S-layer protein contribute to phage specificity in an isoform-dependent manner. In addition, the LMW D2 domain is frequently required, but not always essential for productive infection. Several phages were also able to infect some of the complemented strains despite poor or delayed adsorption, highlighting differences in receptor binding. Interestingly, some phages adsorbed efficiently but failed to infect, showing that the capacity to bind to a host is not always predictive of a successful infection. Our findings reveal the complexity of phage-host interactions in C. difficile and provide new insights into the structural features of the S-layer protein that govern phage binding. These findings will be instrumental in guiding the future design of phage cocktails to target a broad spectrum of C. difficile clinical isolates.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".