Project: Deploying PURIne adjuvants to improve the Fight against StaphYlococcus aureus AMR infections
| Acronym | PURIFY AMR (Reference Number: JPIAMR2024_IMPACT-222) |
| Duration | 01/06/2025 - 31/05/2028 |
| Project Topic | Efforts to improve the effectiveness of existing interventions for antimicrobial resistant (AMR) infections include finding new ways to overcome resistance to licenced antibiotics using adjuvants, or by using antibiotics in new combinations. While antimicrobial chemotherapy targeting the cell wall (e.g. ß-lactams) and folate pathway (e.g. trimethoprim-sulfamethoxazole, TMP-SMX) remains a cornerstone of modern healthcare, resistance to these drugs presents an escalating clinical challenge. We recently reported that purine nucleosides are powerful antibiotic adjuvants that can resensitise methicillin resistant Staphylococcus aureus (MRSA) to ß-lactams. New preliminary data have further identified that purine nucleosides act to downregulate thymidine levels in MRSA cells. Building on this novel mechanistic insight, we revealed that purines potentiate both TMP-SMX (folate is a co-factor for thymidine biosynthesis) and 5-fluorouracil (5-FU), which also disrupts pyrimidine metabolism. In this project we propose to comprehensively evaluate the therapeutic potential of TMP-SMX/purines or 5-FU/purines alone and in combination with ß-lactams against MRSA and other pathogens responsible for wound infections, device-related infections, osteomyelitis, endocarditis and lung infections in people with cystic fibrosis. Further, we will uncover their underlying mechanisms of action and link these mechanisms to antibiotic resistance. This knowledge will help us to improve the effectiveness of licensed antimicrobial drugs, and overcome resistance to ß-lactam antibiotics and TMP-SMX. |
| Website | visit project website |
| Network | JPIAMR-ACTION |
| Call | 5TH JPIAMR-ACTION Joint Call 2024 |