Context

In the 2017 WHO list of the most critical group of bacteria to be controlled are Gram-negative bacterial families. These families’ major resistance mechanism is the production of one or more enzymes called beta-lactamases, which are capable of inhibiting beta-lactam antibiotic agents: penicillin, cephalosporins and, in particular, carbapenems, the antibiotic agent family with the widest activity spectrum, used only in hospitals and generally considered as “last-resort” antibiotics. One approach for countering this resistance is to develop beta-lactamase inhibitors to be co-administered with beta-lactam antibiotics. However, there are no inhibitors available at this time that can inhibit class B beta-lactamase, MBLs (metallo-beta-lactamases), and more specifically the subclass B1 of clinical interest.

Benefits

The team developed and patented molecules with inhibition constants of interest on subclass B1 MBLs. These molecules are capable of both resensitizing bacteria resistant to Meropenem and expressing the MBLs (a carbapenem). These molecules can be regarded as excellent development candidates, and the project is fully in keeping with the current race to find new antibiotics.

Applications

Gram-negative bacteria resistant to beta-lactam antibiotics