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
Author(s)
Costa C., Sirard J.C., Gibson P.S., Veening J.W., Gjini E., Baldry M.
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
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
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