DRIPBEAT · Drug repurposing for inhibiting pathogenic biofilms and potentiating the activity of antibiotics
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-03-07 → 2024-03-06
- EU contribution
- €166,320
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Drug repurposing for inhibiting pathogenic biofilms and potentiating the activity of antibiotics
Cystic fibrosis (CF) is a genetic disease for which the major symptom is abnormally thick, sticky mucus produced by the human body, especially the lungs. It makes patients vulnerable to a toxic bacterium, Pseudomonas aeruginosa, that can be found almost everywhere. P. aeruginosa invading patients’ lungs is trapped by the mucus and grows well in this environment. As P. aeruginosa cells grow, they gather and build themselves a ‘house’ called biofilm for their own protection, making each embedded bacterium almost impossible to kill using antibiotics, and living P. aeruginosa cells constantly damage lung tissue and function. Therefore, disrupting biofilms to revert bacteria to free-floating individuals will significantly enhance their susceptibility to antibiotics. As chronic infections with P. aeruginosa are the main perpetrators of morbidity and mortality in CF patients, this project aims to discover novel anti-biofilm agents as adjunctive therapy that potentiate the efficacy of frequently prescribed antibiotics against P. aeruginosa, thus improving the therapeutic outcomes.
Data: CORDIS, © European Union
Project objective
Bacterial biofilms are closely associated with chronic infections, leading to much higher tolerance to antibiotics and treatment failures. New strategies for biofilm disruption are thus urgently required. Cyclic-di-GMP, a secondary messenger promoting biofilm formation, is a promising drug target. Only few compounds that reduce c-di-GMP levels and inhibit biofilms were identified so far, and most studies were conducted in vitro using standard medium and reference strains. In this project drugs will be repurposed for targeting c-di-GMP and biofilms to increase the antibiotic susceptibility of clinical Pseudomonas aeruginosa strains. Interdisciplinary approaches will be applied, combining next generation sequencing, gene expression pattern in synthetic sputum, protein structural modelling and computational drug docking, lung epithelial cell infection and murine model. This project will increase the accuracy of drug discovery based on c-di-GMP and significantly expand the skillset of an early career researcher with a strong background in the molecular mechanism of c-di-GMP pathway. The new knowledge in human cell culture and murine model obtained in this fellowship will be crucial for the researcher with a long-term interest in infection treatment. The host laboratory at Ghent University (UGent), a leading group in Europe investigating combination therapy against biofilms, offers an excellent atmosphere fostering both technical and transferable skills. The researcher will also benefit from the supervisor’s extensive research network and the numerous training programs provided by UGent to enhance the future career prospects. The research outputs will provide fresh insights into how genetic and environmental conditions influence c-di-GMP pathway (basic science) and how to select more appropriate compounds for biofilm treatment (applied science), and may also be subjected to clinical trials and attract industrial partners for wider applications.
Original text from CORDIS.
Participants
- UNIVERSITEIT GENT · GentCoordinatorBelgium
Links
- View on CORDIS
- DOI: 10.3030/101023767
- https://research.ugent.be/web/result/project/49016780-e165-4ff1-b498-690f0c09ef93/details/dripbeat-41i08921-drug-repurposing-for-inhibiting-pathogenic-biofilms-and-potentiating-the-activity-of-antibio
Data: CORDIS, © European Union