Temperate phages increase antibiotic effectiveness in a <i>Caenorhabditis elegans</i> infection model
Bibliographic record
Abstract
Abstract The bactericidal nature of obligately lytic bacterial viruses (phages) is of increasing interest for the treatment of drug-resistant bacterial infections, either administered alone or in combination with antibiotics. In contrast, temperate phages are largely ignored in a therapeutic context due to their ability to lie dormant within the bacterial host. However, these phages often undergo a lytic cycle. Furthermore, even in their dormant state they can be a considerable burden to the bacterium – most famously by their ability to switch to lytic replication in response to environmental triggers, such as antibiotics, that stress the bacterial host. Recent reports of antibiotics synergizing with temperate phages in vitro , termed “temperate phage antibiotic synergy” (tPAS), present a potentially scalable opportunity to make use of these abundant entities for the treatment of bacterial infections. Here we employ Caenorhabditis elegans as a robust in vivo animal model for testing the efficacy of temperate phages as adjuvants to antibiotics. In vivo , temperate phage Hali alone results in 60% dormancy in the bacterial survivors. However, the antibiotic ciprofloxacin can abolish dormancy of temperate phage Hali - infecting a ciprofloxacin resistant Pseudomonas aeruginosa clinical strain. The phage Hali-ciprofloxacin pairing increased the lifespan of P. aeruginosa infected worms to that of the uninfected control, at doses where neither the phage nor the antibiotic had any effect alone. Complete rescue was also observed in worms infected with a phage-carrying strain treated with the otherwise ineffective antibiotic, supporting that the phage - even in its dormant form - can greatly enhance antibiotic effectiveness. This illustrates potential “accidental” phage therapy when antibiotics are prescribed. Our work establishes C. elegans as a suitable model for studying the in vivo efficacy of tPAS and is the first in vivo demonstration of this synergy, greatly expanding the therapeutic potential of temperate phages.
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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) | 0.001 | 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) | 0.001 | 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".