Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Infectious Diseases Year : 2024

Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance

Abstract

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.
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Friday, November 8, 2024
Embargoed file
Friday, November 8, 2024
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Dates and versions

inserm-04605101 , version 1 (07-06-2024)

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Charlotte Costa, Jean-Claude Sirard, Paddy Gibson, Jan-Willem Veening, Erida Gjini, et al.. Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance. Journal of Infectious Diseases, 2024, pp.jiae239. ⟨10.1093/infdis/jiae239⟩. ⟨inserm-04605101⟩
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