CE19 - Technologies pour la santé

Identification of antibiofilm targets and molecules – BIOScreenTarget

Submission summary

Antibiotic resistance is a major threat to modern medicine and societies (WHO, 2020), especially with the finding that 80% of bacterial infections involve biofilm, which is a microbial community tolerant against all types of antimicrobial agents. In such a clinical context, we must consider developing adapted models, new strategies, and new molecules to treat acute and chronic infections due to biofilm. Our research hypothesis is that a dedicated in vitro model reproducing the major factors of the bone environment, which influence the biofilm structure during bone and prosthesis infection (BPI) will reveal peculiar features of these biofilms that could be identified as antibiofilm targets. Then, this in vitro model will allow the screening of different antibiofilm strategies helping to the identification of essential mechanisms of biofilm. The development of molecules specific to and efficient against bone infections will be facilitated.
Our objective is to fight against BPI biofilm through 1) mid-to-high throughput observations of clinical collection of S. aureus strains to identify “specific” bone context biofilm features and to create a database gathering all potential antibiofilm targets; 2) to screen a bank of natural molecules, synthetic quinolones derivatives and antimicrobial peptides in this same model. Both objectives will lead to highlight molecules with a high affinity towards identified targets thanks to in silico molecular docking or MicroScale Thermophoresis (MST) approach and/or to improve existing molecules to prevent or treat BPI.
Identification of antibiofilm targets or molecules in a suitable and reproducible BPI model developed as a screening tool will help the scientific community to better decipher biofilms in BPI and will facilitate the transfer from in vitro toward in vivo models. New therapeutic strategies will raise to decrease the infection risk occurring after orthopedic surgery.

Project coordination

Fany REFFUVEILLE (Biomatériaux et Inflammation en site Osseux)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CBSA COMMUNICATION BACTERIENNE ET STRATEGIES ANTI-INFECTIEUSES
BIOS Biomatériaux et Inflammation en site Osseux
MEDyC Matrice Extracellulaire et DYnamique Cellulaire
ICMR Institut de Chimie Moléculaire de Reims

Help of the ANR 495,796 euros
Beginning and duration of the scientific project: February 2024 - 42 Months

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