Triggering Toll-Like Receptor 5 Signaling ...
Type de document :
Compte-rendu et recension critique d'ouvrage
DOI :
PMID :
URL permanente :
Titre :
Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance
Auteur(s) :
Costa, Charlotte [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Sirard, Jean-Claude [Auteur correspondant]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Gibson, Paddy [Auteur]
Université de Lausanne = University of Lausanne [UNIL]
Veening, Jan-Willem [Auteur]
Université de Lausanne = University of Lausanne [UNIL]
Gjini, Erida [Auteur]
Instituto Superior Técnico, Universidade Técnica de Lisboa [IST]
Baldry, Mara [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Sirard, Jean-Claude [Auteur correspondant]
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Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Gibson, Paddy [Auteur]
Université de Lausanne = University of Lausanne [UNIL]
Veening, Jan-Willem [Auteur]
Université de Lausanne = University of Lausanne [UNIL]
Gjini, Erida [Auteur]
Instituto Superior Técnico, Universidade Técnica de Lisboa [IST]
Baldry, Mara [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Titre de la revue :
Journal of Infectious Diseases
Pagination :
jiae239
Éditeur :
Oxford University Press
Date de publication :
2024-05-08
ISSN :
0022-1899
Mot(s)-clé(s) en anglais :
Flagellin
Toll-like receptor 5
airways
innate immunity
Streptococcus pneumoniae
antibiotic resistance
infection dynamics
modelling
Toll-like receptor 5
airways
innate immunity
Streptococcus pneumoniae
antibiotic resistance
infection dynamics
modelling
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Abstract Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) ...
Lire la suite >Abstract Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) improves the treatment of primary pneumonia or superinfection caused by AMX-sensitive or AMX-resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and antibiotic-resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. A mathematical model was developed that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.Lire moins >
Lire la suite >Abstract Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) improves the treatment of primary pneumonia or superinfection caused by AMX-sensitive or AMX-resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and antibiotic-resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. A mathematical model was developed that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Projet Européen :
Source :
Date de dépôt :
2024-06-11T02:13:59Z