Synergistic interactions among <i>Burkholderia cepacia</i> complex (Bcc)-targeting phages reveal a novel therapeutic role for lysogenization-capable (LC) phages
Notice bibliographique
Résumé
ABSTRACT Antimicrobial resistance is an imminent danger to global public health and threatens virtually all aspects of modern medicine. Particularly concerning are the species of the Burkholderia cepacia complex (Bcc), which cause life-threatening respiratory infections among patients who are immunocompromised or afflicted with cystic fibrosis, and are notoriously resistant to antibiotics. One promising alternative being explored to combat Bcc infections is phage therapy (PT) - the use of phages to treat bacterial infections. Unfortunately, the utility of PT against many pathogenic species, including the Bcc, is limited by the prevailing paradigm of PT: that only obligately lytic phages, which are rare, should be used therapeutically - due to the conviction that so-called ‘lysogenic’ phages do not reliably clear bacteria and instead form lysogens to which they may transfer antimicrobial resistance or virulence factors. In this study, we argue that the tendency of a lysogenization-capable (LC) phage to form stable lysogens is not predicated exclusively on its ability to do so, and that this property, along with the therapeutic suitability of the phage, must be evaluated on a case-by-case basis. Concordantly we developed several novel metrics - Efficiency of Phage Activity (EPA), Growth Reduction Coefficient (GRC), and Lysogenization Frequency ( f (lys) ) and used them to evaluate eight phages targeting members of the Bcc. We found that while these parameters vary considerably among Bcc phages, a strong inverse correlation exists between lysogen-formation and antibacterial activity, indicating that certain LC phages may be highly efficacious on their own. Moreover, we show that many LC Bcc phages interact synergistically with other phages in the first reported instance of mathematically defined polyphage synergy, and that these interactions result in the eradication of in-vitro bacterial growth. Together, these findings reveal a novel therapeutic role for LC phages, and challenge the current paradigm of PT. IMPORTANCE The spread of antimicrobial resistance is an imminent threat to public health around the world. Particularly concerning are the species of the Burkholderia cepacia complex (Bcc), which cause life-threatening respiratory infections and are notoriously resistant to antibiotics. Phage therapy (PT) is a promising alternative being explored to combat Bcc infections and antimicrobial resistance in general, but the utility of PT against many pathogenic species, including the Bcc, is restricted by the currently prevailing paradigm of exclusively using rare obligately lytic phages - due to the perception that ‘lysogenic’ phages are therapeutically unsuitable. Our findings show that many lysogenization-capable (LC) phages exhibit powerful in vitro antibacterial activity both alone and through mathematically defined synergistic interactions with other phages, demonstrating a novel therapeutic role for LC phages and therefore challenging the currently prevailing paradigm of PT.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».