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
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Publication Status: aheadofprint
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 improves the treatment of primary pneumonia or superinfection caused by amoxicillin-sensitive or -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 -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. Finally, we developed a mathematical model 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
Streptococcus pneumoniae, Flagellin, Toll-like receptor 5, airways, antibiotic resistance, infection dynamics, innate immunity, modelling
Pubmed
Web of science
Open Access
Yes
Create date
10/05/2024 14:59
Last modification date
27/07/2024 6:00