Vaccins et agents thérapeutiques à base de sucres contre les bactéries Gram-négatif

 

Charles Gauthier

Institut national de la recherche scientifique [INRS]

 

Domaine : maladies infectieuses et immunitaires

Programme Chercheurs-boursiers - Junior 2

Concours 2018-2019

The ever-increasing antibiotic resistance of bacteria is becoming a major health problem worldwide. No new class of broad-spectrum antibiotics has been discovered since the 1960s. In allowing the eradication of numerous bacterial infections, vaccination stands as an effective alternative to antibiotics. Bacteria express a dense network of polysaccharides at their surface, which act as target antigens of the immune response and thus represent exquisite vaccine candidates. However, access to these polysaccharides is complicated because of potential biological contaminations and issues regarding the large scale culture of pathogenic bacteria. Our research program aims, on one hand, to devise novel synthetic pathways allowing access to bacterial polysaccharides by using multi-step chemical synthesis and, on the other hand, to develop vaccines, diagnostic tools, and therapeutic agents based on these synthetic molecules.

Synthetic approaches will be developed to generate mimics of the main surface polysaccharides from Burkholderia pseudomallei, the causative agent of melioidosis and a potential bioterrorist threat, and Campylobacter jejuni, the world's leading cause of bacterial diarrhea. The synthesized compounds will be coupled to an immunogenic protein and evaluated for their vaccine potential. Furthermore, novel broad spectrum antibiotics able to destabilize the membrane of pathogenic bacteria by inhibition of the biosynthesis of their surface polysaccharides will be prepared and tested for their antibacterial activity. The proposed research program could trigger the discovery of sugar-based medicines that could find applications to kill resistant pathogens and to develop novel diagnostics and vaccines.