SLPI inducers

Identifying inducers of secretory leukocyte protease inhibitor (SLPI) to limit the use of antibiotics and the spread of antibiotic resistance



Résumé
The spread of multi-antimicrobial drugs resistant pathogens is a major health concern. Given the difficulty to develop novel antibiotics, there is an urgent need for alternative strategies to overcome this challenge.Here, we propose that small molecules that increase the expression of the secretory leukocyte protease inhibitor (SPLI), a protein with broad antimicrobial activities that also has anti-inflammatory and tissue healing properties might provide a unique approach to tackle this global health problem. In order to identify small molecules increasing SLPI-expression in relevant cell types, a screening of the French National Chemical Library (55,000 compounds) using a flow cytometry approach will be performed. After a hit-to-lead optimization, in vitro characterization and in fine in vivo proof of concept will be achieved. The ultimate goal of this project is to identify compounds that increase SLPI expression in a relevant manner in vivo to minimize the amount and duration of anti-microbial drugs needed to clear an infection.

Mots-clés
High-throughput screening, Medicinal chemistry, Infectious disease, antimicrobial resistance, nosocomial infection

Partenaires du projet

INSB
FILLATREAU Simon
(UMR8253) Paris France
INC
Mahuteau-Betzer Florence
Chimie, Modélisation, Biophysique et Biochimie (UMR9187) France
Sibyline BORZAKIAN/site Biorender
Crédit photo : Sibyline BORZAKIAN/site Biorender