No novel antibacterial drug classes have been discovered and developed for clinical use since 1987. This lack of innovation in antimicrobial research has resulted in limited new options to address multi-drug-resistant bacteria like Gram-negative (Gram-) bacteria. Infections by multi-drug-resistant Gram- bacteria are particularly hard to treat because the impermeability of the outer membrane restricts access by existing standard-of-care antibiotics. The goal of the BREAKthrough project is, therefore, to destabilise the outer membrane and make it permeable, sensitising the Gram- bacteria to antibiotics.
BREAKthrough aims to sensitise bacteria towards new and existing drugs.
Prof. Jean-François Collet
UCLouvain, BREAKthrough coordinator
To make multi-drug-resistant Gram- bacteria vulnerable to standard-of-care antibiotics, their outer membrane, their barrier to the outer world, needs to be broken. For this purpose, the project will target three key protein systems that are essential to maintain the outer membrane. Defects in any of these three targets have been shown to increase the permeability of the outer membrane, allowing a large variety of drugs to enter the cell. BREAKthrough aims to deliver molecules that inhibit these three protein machineries.