NOVEL APPROACHES FOR PREVENTION/ERADICATION OF PSEUDOMONAS AERUGINOSA LUNG INFECTIONS IN MURINE MODELS
Notice bibliographique
Résumé
Pseudomonas aeruginosa is one of the top three causes of opportunistic human infections in different categories of patients. Antibiotics are used as first line drugs for the treatment of these infections. However, frequently observed inefficacy of these treatments is linked to the high levels of intrinsic and acquired resistance of P. aeruginosa to these agents. Unfortunately during the last decades few novel anti-pseudomonas drugs have arrived to clinical phases. Moreover, in the past, several vaccine candidates against P. aeruginosa have been tested in pre-clinical trials, few have reached clinical phases but none of these has obtained market authorization. Thus, this scenario highlights the need of new therapeutic options for the prevention/eradication of P. aeruginosa. In the first part of this work the efficacy of a novel Protein Epitope Mimetic antibiotic named New Chemical Entity (NCE) was assessed in murine models of P. aeruginosa acute and chronic airways infection, including CFTR-deficient mice. A comparison between different administration routes (systemic versus pulmonary) was also considered. NCE demonstrated a remarkably efficacy in reducing the bacterial load and the inflammation in the lung when administered locally in all murine models tested. The efficacy of this novel antibiotic peptide was superior to ciprofloxacin, one of the current available treatments. Moreover pharmacokinetic studies confirmed that NCE reached favorable concentrations in the lung after pulmonary administration. These results supported the development of NCE as a potential novel inhaled therapy to treat P. aeruginosa airways infections. In the second part of this work, novel vaccine candidates against P. aeruginosa, identified by the combination of advanced whole genomic approaches including the ?reverse vaccinology?, were tested in murine models of acute pneumonia. 32 vaccine candidates were tested for their ability to protect against a lethal dose of P. aeruginosa. 10 proteins showed an increase in the survival curves when compared with a negative control group. Further characterization suggested that the vaccine candidates were immunogenic, expressed in bacterial culture and surface exposed. When combinations of two proteins were tested in murine models, five of them showed a statistically significant increase in both the survival curves and mean survival time compared with a negative control group. The highest protection rate (50%) was achieved by the combination of two unknown proteins. Overall these results suggested that the combination of comparative genome analysis and innovative methods in vaccine design are valid tools for the identification of novel vaccine candidates against P. aeruginosa.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 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 | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».