The massive scope of antimicrobial resistance (AMR) has prompted scientists to investigate alternatives to antibiotics for the treatment of patients afflicted by multidrug-resistant (MDR) bacteria. We have designed a unique inhibitor of the copper P-type ATPase, 3A11, and developed it to its preclinical phase.
We have shown it to be effective against several major Gram-positive pathogens, including MDR bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). This is of great importance, due to the current lack of treatment options for VRE infections. To test the efficacy of our inhibitor, 3A11, against a plethora of strains, a vast panel of clinical isolates from the repositories of the project partners will be studied. The antimicrobial effects of 3A11 against this panel will be assessed and investigated in vitro to better understand the underlying molecular mechanisms of action. Additionally, to have a better model of the interactions between 3A11 and host cells, the bactericidal effects of this inhibitor will be analysed both in human cells and in mice.
A better understanding of the effects of 3A11 on bacterial cells and its molecular mechanisms of resistance will assess the suitability of this inhibitor as a non-antibiotic agent in the fight against AMR.
Project partners
- Shilpa Ray, Karolinska Institutet, Sweden (Coordinator)
- Gerard Lina, Centre International de Recherche en Infectiologie, France
- Vincent Cattoir, University of Rennes 1, France
- Anne Santerre Henriksen, Maxel Consulting ApS, Denmark
- Anders Rhod Larsen, Statens Serum Institut, Denmark
