Project CARBAMAT aims to fight antibiotic resistance by developing inhibitors of carbapenemase, molecules produced by certain bacteria and causing resistance to antibiotics. This project is the result of research carried out at Paris-Sud University, CNRS, CEA, INSERM and the University Hospital of Île-de-France.
Antibiotic resistance is a major public health problem worldwide, especially since the emergence of bacteria that are resistant to several antibiotics, or even to the entire therapeutic arsenal. The number of these multi-resistant bacteria is increasing exponentially and their geographical location is also expanding. To fight antibiotic resistance, the CARBAMAT project aims to develop two original families of carbapenemase inhibitors.
Seeking to tackle a real societal challenge, this project will allow the scientists to obtain a drug candidate. Carbapenemases are the enzymes produced by bacteria to degrade all β-lactams, including carbapenems—last-resort antibiotics used against serious Gram-negative bacterial infections that show multiple resistance to antibiotics. The inhibitors developed within project CARBAMAT would make bacteria once again sensitive to antibiotics of the β-lactams type.
Their innovative aspects are:
- Broad activity spectrum made possible by a molecular design approach based on molecular modeling: they act on several classes of carbapenemases;
- Low sensitivity to resistance: beyond existing resistances, their development also takes future potential resistances into account (identified by joint efforts of the microbiology and molecular modeling teams).
Initiated in 2012 by teams from the Laboratory of Excellence in Drug Discovery and Therapeutic Innovation (LERMIT LabEx) at Paris-Saclay University, the project federates multidisciplinary and complementary laboratories, notably those of Alain Pruvost and Jean-Christophe Cintrat from the Frédéric-Joliot Life Sciences Institute—two laboratories specialized in drug metabolism and medicinal chemistry, respectively.