Triggering Toll-Like Receptor 5 signaling during pneumococcal superinfection prevents the selection of antibiotic resistance.
J Infect Dis
; 2024 May 08.
Article
em En
| MEDLINE
| ID: mdl-38716762
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.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França