The G-Q-reat ESKAPE · Druggability of G-quadruplexes, promising modulators for antimicrobial resistance
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-09-01 → 2025-08-31
- EU contribution
- €172,750
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Druggability of G-quadruplexes, promising modulators for antimicrobial resistance
Antimicrobial resistance (AMR) is one of today’s most pressing global health threats, responsible for millions of deaths every year. "The G-Q-reat ESKAPE" project (Druggability of G-quadruplexes, promising modulators for antimicrobial resistance) explored an entirely new class of bacterial drug targets, namely bacterial G-quadruplexes (G4s). These are four-stranded DNA structures that can regulate key genes involved in replication, virulence and antibiotic resistance. "The G-Q-reat ESKAPE" project combined computational chemistry, molecular dynamics (MD) simulations and biophysical experiments to identify, model and validate bG4s as potential antimicrobial targets, focusing on six priority pathogens of the WHO “ESKAPE” list: Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae.
Data: CORDIS, © European Union
Project objective
The antimicrobial resistance (AMR) is an underrated problem promoted by widespread misuse and massive use of antibiotics. Thus, the health systems are facing enormous costs to treat nosocomial infections due to AMR bacteria. In particular, six highly virulent bacteria (E.S.K.A.P.E.) are the main responsible for worldwide nosocomial infections. In the last years, our research strategies to discover and develop new clinically relevant antibiotics lacked effectiveness. As a result, we are unable to efficiently treat AMR infections and are unprepared to face an AMR bacteria outbreak. One possible strategy is to target bacteria G-quadruplexes (bGQs) which are highly conserved DNA/RNA secondary structures pivotal for bacteria duplication, transcription and translation. This strategy is particular effective because, when a new pathogen emerges, its DNA/RNA genome is first disclosed through sequencing, hence the ability of quickly designing new drug candidates based only on this information will be a powerful tool to face a new epidemic/pandemic. Furthermore, the human GQs (hGQs) were largely investigated as possible target for anticancer treatment thus the interest in bGQs raised later and with less intensity than hGQs. In addition, most GQs modulators bind G-quartets top by π-stacking interactions and the druggability of GQs loops/grooves was still not addressed. In this context, the multidisciplinary of G-Q-reat ESKAPE project aims to provide a novel and effective strategy to contrast AMR by targeting bGQs and to expand the knowledge on bGQs.
Original text from CORDIS.
Participants
- UNIVERSITA DEGLI STUDI DI SIENA · SienaCoordinatorItaly
Links
- View on CORDIS
- DOI: 10.3030/101106871
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5093f5648&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5214d4f5e&appId=PPGMS
Data: CORDIS, © European Union