University of Liverpool researchers are part of a £1.1m project aimed at improving the effectiveness of existing treatments against antimicrobial resistance (AMR).
Infections caused by antimicrobial resistant pathogens pose a major and growing threat to public health. This new project, funded through the Joint Programming Initiative on Antimicrobial Resistance (JPI-AMR), brings together researchers from the University of Liverpool, the University of Galway, the University of Muenster and the University Hospital Muenster.
The interdisciplinary team will explore new ways to overcome resistance by developing novel antibiotic adjuvants - chemicals designed to help an antibiotic to work more effectively in the treatment of bacterial AMR infections.
The antibiotic adjuvants developed in this project are based on purine nucleosides, which are essential building blocks of nucleic acids that play important roles in cellular signalling and metabolism.
The project will evaluate the therapeutic effectiveness of purine nucleosides in restoring or enhancing the activity of two distinct classes of antibiotics: penicillin-type antibiotics (β-lactams), which target the cell wall, and trimethoprim-sulfamethoxazole (TMP-SMX) which blocks folate and DNA synthesis in bacteria. Purine nucleosides have demonstrated potent activity as adjuvants which can resensitise MRSA to oxacillin and other β-lactam antibiotics.
Researchers will test the therapeutic potential of purine adjuvants - both on their own and in combination with β-lactam antibiotics, against MRSA and other bacteria that cause wound and device-related infections, osteomyelitis, endocarditis and lung infections in people with cystic fibrosis.
The team also aims to uncover how these compounds work at a molecular level and how their mechanism of action relate to antibiotic resistance. This knowledge could lead to more effective use of existing antibiotics and offer new strategies to manage AMR.
Professor Aras Kadioglu, Head of the Department of Clinical Infection, Microbiology and Immunology (CIMI) and Liverpool project lead said: “We all know that the burden of infections caused by AMR pathogens is a leading threat to public health and a significant global problem, but what if we could treat AMR infections with the antibiotics we already have?”
“The central aim of this project is to find novel ways to maintain the effectiveness of existing antibiotics such as β-lactams, by use of novel adjuvants, which can potentiate antibiotic activity and disrupt bacterial resistance mechanisms.”
“I am delighted that JPI-AMR has funded this project, allowing us to work together again with our long-time collaborator Professor James O’Gara (and colleagues at the University of Galway) who have been leading the way on repurposing antibiotics. I believe our new antibiotic adjuvant approach may be an important part of overall efforts to address the global AMR crisis.”