Olivier Renaudet

Host institution: University Grenoble Alpes

Laboratory: DCM

Call for Projects: Proof of Concept (POC2)

Project name: PATHO-LEGO – All-in-one supramolecular approach as an innovative anti-infectious strategy

Amount: 0.150 M€

Description: 

Despite the large therapeutic arsenal available to fight bacterial infections, the development of new anti-infectious strategies is a major public health concern. Pathogens have indeed developed a variety of Multi Drug Resistance mechanisms to escape destruction. To circuvment these problems, a few promising alternatives have been proposed. A first one focuses on the bacterial adhesion step to the host cells which involves multivalent interactions between the glycocalix and bacterial adhesins. Molecular constructs displaying clusters of carbohydrates have been shown to efficiently compete with these complex recognition processes, thus having the potential to prevent this key step of the bacterial infection. The recruitment of natural antibodies (NAbs) present in the human bloodsteam against biological targets to stimulate their destruction by the immune system is another alternative to fight pathogens. This approach is based on the utilization of bimodal molecules (namely ARGs, Antibody Recruiting Glycodendrimers) which are composed of two recognition domains, one for NAbs and one for receptors expressed by the pathogen. The potential of this “recruiting strategy” was demonstrated recently in the PI’s team in the context of cancers where NAbs have been efficiently redirected against tumors (ERC CoG LEGO and ERC PoC THERA-LEGO). For the first time, PATHO-LEGO will take advantage of these two “antiadhesive” and “recruitment” strategies simultaneously to fight resistant strains of Pseudomonas aeruginosa. We aim at developing hybrid ARGs that will block extracellular process that P. aeruginosa uses to infect host cells on the one hand, and that will redirect NAbs against the bacteria to induce their immune-mediated clearance on the other hand. With this unprecedented approach, we will be able to both prevent infection and kill the targeted resistant bacteria to optimize the antibacterial effect.