The G-Q-reat ESKAPE | Druggability of G-quadruplexes, promising modulators for antimicrobial resistance

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101106871
Start date: 01-09-2023
End date: 31-08-2025
Total budget - Public funding: - 172 750,00 Euro
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Original description

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.

Status

SIGNED

Call topic

HORIZON-MSCA-2022-PF-01-01

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2022-PF-01
HORIZON-MSCA-2022-PF-01-01 MSCA Postdoctoral Fellowships 2022