Triggering Toll-Like Receptor 5 Signaling ...
Document type :
Compte-rendu et recension critique d'ouvrage
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Title :
Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance
Author(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]
Journal title :
Journal of Infectious Diseases
Pages :
jiae239
Publisher :
Oxford University Press
Publication date :
2024-05-08
ISSN :
0022-1899
English keyword(s) :
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
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [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) ...
Show more >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.Show less >
Show more >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.Show less >
Language :
Anglais
Popular science :
Non
European Project :
Source :
Submission date :
2024-06-11T02:13:59Z