NO-ESKAPE New Strategies for Overcoming the ESKAPE Pathogens
Natural product inspired antibiotics to address resistance
- 2017 - 2022
- Nathaniel Martin
- European Research Council (Grant agreement no. 725523)
Antibiotic resistance poses an alarming threat to global health. Most worrisome are the so-called “ESKAPE” pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and Enterobacter species), a collection of organisms capable of escaping the effects of almost all conventional antibiotics. Key to combating drug-resistant bacteria is the identification of new antibacterial targets and the ability to exploit these targets with novel and unconventional antibiotics.
To tackle the Gram-positive ESKAPE pathogens a number of new approaches to interfering with bacterial cell wall biosynthesis will be examined. Specifically, novel (semi)synthetic compounds capable of binding to and sequestering various bacterial cell wall precursors will be prepared and their antibiotic activity assessed.
To address the Gram-negative ESKAPE pathogens, inhibitors of the metallo-beta-lactamase enzymes responsible for much of their antibiotic resistance will be pursued. These inhibitors will be achieved via a combination of rational design strategies and innovative natural product screening approaches.