Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.
Details
Serval ID
serval:BIB_DBC6497572C4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.
Journal
The Journal of infectious diseases
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Publication state
Published
Issued date
15/11/2024
Peer-reviewed
Oui
Volume
230
Number
5
Pages
e1126-e1135
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Superinfection/microbiology, Superinfection/drug therapy, Streptococcus pneumoniae/drug effects, Toll-Like Receptor 5/metabolism, Toll-Like Receptor 5/agonists, Anti-Bacterial Agents/pharmacology, Anti-Bacterial Agents/therapeutic use, Signal Transduction/drug effects, Flagellin, Pneumococcal Infections/drug therapy, Pneumococcal Infections/microbiology, Pneumococcal Infections/immunology, Pneumococcal Infections/prevention & control, Amoxicillin/pharmacology, Amoxicillin/administration & dosage, Drug Resistance, Bacterial, Humans, Animals, Models, Theoretical, airways, antibiotic resistance, flagellin, infection dynamics, modelling
Pubmed
Web of science
Open Access
Yes
Create date
10/05/2024 14:59
Last modification date
20/11/2024 7:16